CA1256862A - Aromatic heterocyclic derivatives and process for their preparation - Google Patents

Abstract

The invention relates to compounds of formula (I): <IMG> (I) in which R1 = -CH3, -CH2OH or <IMG>, where R3 = H or -OR4, where R4 = H, alkyl or mono or polyhydroxyalkyl , or R3 = <IMG> where r 'and r "= H, lower alkyl or taken together form a heterocycle, R2 = H or -CH3, Ar = aromatic radical, Y == CH- or a nitrogen atom, and X = O, S or <IMG> where R8 = H, lower alkyl or lower alkoxycarbonyl. The invention also relates to the process for the preparation of the compounds of formula (I). These compounds of formula (I) are useful in the field cosmetics, especially for body and hair hygiene.

Description

The subject of the present invention is new aromatic heterocyclic derivatives, their key process and their use in cosmetics.
Given their chemical structure, heterocyclic aromatic compounds according to the invention will be referred to below as "Hetero-differines ".
The hetero-differins according to the invention can be represented by the general formula (I):

R (I) in which: 2 Rl represents (i) -CH
(ii) -CH20H
(iii) -C-R3 R3 represents a hydrogen atom, the radical -OR4, R4 representing a hydrogen atom, a radical alkyl having from 1 to 20 carbon atoms, a _, 5 ', ~, ~

8 ~
mono or polyhydroxyalkyl radical or R represents the radical 3 \ r'l r 'and r "representing a hydrogen atom, an alkyl radical inferler or taken together form a heterocycle, R ~ represents a hydrogen atom or the radical -CH3, Ar represents an aromatic radical corresponding to one of the for ~ ules following:
(a) CH ~ (A) ~ b) CH ~ ~ (B) Z being O or S
(c) ~
S ~ (C) R5 representing a lower alkyl radical and (d) ~

R60 ~ (D) R6 representing a hydrogen atom or an alkyl radical having 1 with 10 carbon atoms and R7 representing a branched alkyl radical having 4 with 12 carbon atoms or a cycloalkyl radical.
Y represents CH or a nitrogen atom, and X represents an oxygen atom, a sulfur atom or the radical -NR ~, R ~ representing a hydrogen atom, a lower alkyl radical or a lower alkoxycarbonyl radical, BSB / JD / EL / ~ L BR.13347 subject on the one hand that when Y represents CH and X represents an oxygen ~ ene or sulfur atom, Ar is different from a radical of formula (C) dar ~ s which R5 ~ -CH3 and secondly that when Y represents an atom of nitrogen ee X ee represents an oxy ~ ene atom, Ar is different from a radical of formula (C ~ or of formula (D) in which R6 represents an alkyl radical having from 1 to 4 carbon atoms and R7 represents a branched alkyl radical having 4 to 12 carbon atoms.
By lower alkyl radical is meant a radical having 1 to 6 carbon atoms, nota ~ ment a methyl, ethyl, isopropyl radical, butyl and tert-butyl.
By monohydroxyalkyl radical, we must understand a radical having 2 or 3 carbon atoms, in particular a 2-hydroxyethyl radical, and 2-hydroxypro-pyle.
The term “polyhydroxyalkyl radical” should be understood to mean a radical derived from glycerol, pentaerythritol or mannitol.
By lower alkoxycarbonyl radical is meant a radical having an alkyl chain, branched or not, of 1 to 4 carbon atoms. From preferred lower alkoxycarbonyl radicals that may be mentioned: the radical methoxy carbonyl, ethoxy carbonyl, isopropoxy carbonyl and tert-butoxy carbonyl.
When the radicals r 'and r "taken together form a heterocycle, this can be a piperidino, piperazino, morpholino or pyrroli- radical.
dlno.
When the radical R7 represents a cycloalkyl radical, the latter is preferably a cyclohexyl, 1-methyl cyclohexyl or adamantyl radical.
According to a particular embodiment, the hetero-differins according to the invention, correspond to the general formula (II):

CH ~ Y ~ Rl (II) in which :
R represents -CH OH or -C-R3 R3 representing -O-R4 or - N

BSB / JD / EL / ~ L BR.13347 ~ 6 ~
R4 representing a hydrogen atom, a radical - ~ H3 or -CH2CH20 ~]
r 'and r "identical or different representing a hydrogen atonle, a lower alkyl radical or taken together form a morpholino ring Y represents CH or a nitrogen atom and X represents a sulfur atom, an oxygen atom 0 ~ R8, R8 being a hydrogen atom, rac1ica ~. -CH3 or -C02 tert-butyl: at the general formula III:

3 ~ X ~ ~ 1C-o-R4 (III) in which :
R4 represents a hydrogen atom or a radical -CH3 Y represents CH or a nitrogen atom and X represents a sulfur atom, an oxygen atom or N-R8, R8 being a hydrogen atom or the radical -C02 tert-butyl; or at the general formula (IV ~: y ~ CO-R4 in which :
R4 represents a hydrogen atom or a radical -CH3 R6 represents the radical -CH3 or CloH2l R7 represents the tert-butyl radical, dimethyl-l, l decyl or adamantyle Y represents CH or a nitrogen atom and X represents a sulfur atom, an oxygen atom or ~ -R8, R8 being a hydrogen atom.
Among the preferred hetero-differentins of formula (I) one can include the following:
- methyl 2- (p-tert-butylphenyl) -6-benzo (b) thiophenecarboxylate, the 2- (p-tert-butylphenyl) -6-benzo (b) thiophenecarboxylic acid, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzo (b) thiophene-BSB / JD / EL / ML BR.13347 methyl carboxylate, 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzo acid (b) ~ -thiophenecarboxylic, methyl 2- (p-tert-butylphenyl) - benzo (b) furarmecarboxylate, 2- ~ p-tert-butylphenyl) -benzo (b) f ~ lrannecarboxyllque acid, 2- (5,6,7,8 ~ téerahydro-5,5, ~, 8-tétramethyl-2-naphtyl) -6-benzo (b) ~ uranne-methyl carboxylate, 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-bellzo (b) acid -carboxylic furan, l-ter-butoxycarbonyl-2- (p-tert-butylphenyl) -6-indolecarboxylate methyl 2- (p-tert-butylphenyl) -6-indolecarboxylic acid, l-tert-butoxycarbonyl-2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-methyl indolecarboxylate, 2- (5,6,7,8-tetrahydro-5,5,8,8, -tetramethyl-2-naphthyl) -6-indolecarboxylate methyl, 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) acid -6-indolecarboxylic, 1-methyl-2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-indole-methyl carboxylate, 1-methyl-2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6- acid indolecarboxylic, methyl 2- (p-tert-butylphenyl) -5-benzimidazole carboxylate, 2- (p-tert-butylphenyl) -5-benzimidazole carboxylic acid, 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -benæimidazole-methyl carboxylate, 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -benzimidazole- acid carboxylic, 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzoxazole-carboxyl ~ te of methyl, 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 naphthyl) -6-benzoxazole- acid carboxylic, acid morpholide 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naph-tyl) -6-benzoxazole carboxylic, 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 naph-) ethylsmide tyl) -6-benzoxazole carboxylic, 2-hydroxyethyl ester of 2- (5,6,7,8-tetrahydro-5,5,8,8-t ~ tra-methyl-2-naphthyl) -6-benzoxazole carboxylic, alcohol 2- (5,6,7,8-tetrahydro-5,5, 8,8-tetramethyl-2-naphthyl) -6-benzoxazolyl BSB / JD / EL / ML BR.13347 ~ s ~
methyl, 2-L 3- (1-adamantyl ~ -4-methoxyphenyl] -5-benzi- acid methyl ester carboxylic midazole, the methylster ~ as ac ~ of 2-L 3- (1-adamantyl) -4 methoxyphenyl ~ -6-benzo-carboxylic xazole J
2- [3- (1- ~ damantyl) -4-methoxyphenyl] -6-benzoxazole carboxylic acid, 2- (3- ~ 1-adamantyl) ~ -4 decyloxyphenyl ~ -6-ben- methyl ester carboxylic zoxazole, 2 L3- (1-adamantyl) -4-decyloxyphenyl] -6-benzoxazole carboxylic acid, 2- L 3- (1-adamantyl) -4-methoxyphenyl] -6 benzo- methyl ester (b) carboxylic furan J
2-L 3- (1-adamantyl) -4-methoxyphenyl ~ -6-benzo (b) furan carboxy- acid lique, 2- methyl ester of 2- L3- ~ 1-adamantyl) -4 methoxyphenyll -6-benzo-(b) carboxylic thiophene, 2- L3- (1-adamantyl) -4-methoxyphenyl] -6-benzo (b) thiophene carboxy- acid lique, 2- (3-tert-butyl-4-methoxyphenyl) -6-benzo acid methyl ester ~ b) -carboxylic furan, 2- (3-tert-butyl-4-methoxyphenyl) -6-benzo (b) furan carboxylic acid, 2- ~ 3- (1,1-Dimethyldecyl) -4-methoxyphenyl acid methyl ester ~
-6-benzo (b) carboxylic furan, 2- t3- (1,1-dimethyldecyl) -4-methoxyphenyl ~ -6-benzo (b) furan acid carboxylic, 2- L 3- (1-adamantyl) -4-methoxyphenyl] -5-benzimidazole carboxylic acid, 2- L3- (1-adamantyl-4-hydroxyphenyl ~ -5-benzi-) methyl ester carboxylic midazole, 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl- acid methyl ester

2-naphthyl) -6-benzothiazole carboxylic acid, 2- ~ 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzothiazole- acid carboxylic, and the methyl ester of 2- (4,4-dimethyl-2,3-dihydro-1-benzopyran-) acid 6-yl) -5 benzimldazole carbox -BSB / JD / EL / ML BR.13347 6 ~

The present invention also relates to a process for the preparation of heterocyclic aromatic compounds ticks or hetero-diferins having the following Formula:

~ X ~ (I) in which:
- Rl represents:
(i) -CH3 (ii) -CH20H
(iii) -C R3 R3 represents a hydrogen atom, the radical -OR, R representing a hydrogen atom, a radical alkyl having from 1 to 20 carbon atoms, a mono radical or polyhydroxyalkyl, or R3 represents the radical -N /
r "
r 'and r "representing a hydrogen atom, a lower alkyl radical or taken together form a heterocycle, - R2 represents an atom of l ~ ydrogen or the radical -CH3, - Ar represents a corresponding aromatic radical -one of the following formulas:

(a) CH3 CH3 ~ (A)

3 3 (b) H3 3 ~ ~ (B) Z being O or S

(c) ~ /
ll (C) R5 ~
R5 representing a lower alkyl adical and (d) ~
~ I (D) R6 representing a hydrogen atom or a alkyl radical having from 1 to 10 carbon atoms and R7 representing a branched alkyl radical having from 4 to 12 carbon atoms or a cycloalkyl radical, Y represents CH or a nitrogen atom, and X represents an oxygen atom, an atom of sulfur or the radical ~ N R8, R8 representing a hydro-gene, a lower alkyl radical or an alkoxycar- radical . ,.
'~' .

, 1 ~ 5 ~ 86; ~

lower bonyle, on the one hand only when Y represents CH and X represents an oxygen or sulfur atom, Ar is different from a radical of formula (C) in which R5 = -CH3 and on the other hand that when Y represents a nitrogen atom and X represents an oxygen ato ~ e, Ar is different from a radical of formula (C) or of formula (D) in which R6 represents an alkyl radical having from 1 to 4 atoms of carbon and R7 represents a branched alkyl radical having from 0 4 to 12 carbon atoms;
characterized by the fact that it consists in making react an aromatic carboxylic acid derivative of formula:

/ C \ (1) Ar Q
in which:
Ar is as deEini above and Q represents OH or Cl, (a) either on a carboxylic acid derivative of formula:

~? ~ R4 in which:
R2 and R4 are as defined above and X
represents, NH, -O-or-S-, and to carry out a cyclisa-dehydrating action in the presence of an acid catalyst, (b) either on a carboxylic acid derivative of formula:

- 10 ~

(4) ~ OR ~
O

in which:
R2 and R4 are as defined above and X represents ~ NH, -O-or-S-, and to carry out a bromination of the substituent methyl in position 4 and then to cyclize the intermediate derivative carrying a phosphonium group or phosphinyl according to the conditions of the Wittig reaction, and possibly to transform, according to known methods, the so-called compounds obtained with a view to obtaining any of the other meanings of the radical Rl.
In formula (I) we must understand by:
- lower alkyl radical, a radical having from 1 to 6 carbon atoms, in particular a methyl radical, ethyl, isopropyl, butyl and tert-butyl.
- monohydroxyalkyl radical, a radical having 2 to 3 carbon atoms, in particular a 2-hydroxyethyl radical, and 2-hydroxypropyl.
- polyhydroxyalkyl radical, a derivative radical glycerol, pentaerythritol or mannitol.
- lower alkoxycarbonyl radical, a radical having a branched or unbranched alkyl chain of 1 to 4 atoms of carbon, in particular the methoxy carbonyl, ethoxy radical carbonyl, isopropoxy carbonyl or tert-butoxy carbonyl.
When the radicals r 'and r "taken together 3 ~ form a heterocycle, it can be a radical piperidino, pipérazino, morpholino or pyrrolidino.
When the radical R. ~ represents a radical cycloalkyl, this is preferably a cyclo radical hexyl, l-methyl cyclohexyl or adamantyle.

The first embodiment of the method according to the invention can be represented by the sch ~ my reaction following:
Diagram I

o H; ~ N ~

Ar Q l1X ~ OR ~

(1) R2 (2) A ~ / ~ O OR4 R2 Q = OH or Cl ~ 3) X = `NH, -O-ou-S-This process, which is particularly suitable for the preparation of the compounds of formula (I) in which Y represents a nitrogen atom, consists in making react an aromatic carboxylic acid derivative of formula (1) on an aromatic carboxylic acid derivative of formula (2) carrying an amino radical in position 4 and a radical amino, hydroxy, or thio in position 3.
Preferably, a reaction is carried out.
acylation, in the presence of a tertiary amine, between a composed of formula:

/ \
Ar Cl and a carboxylic acid ester of formula:

2 ~

HX '' ~ ~, OR'4 R2 being as defined above, R'4 representing a alkyl radical having from 1 to 20 carbon atoms and X ' representan., NH or -S- ~ then a cyclization reactlon desiccant of the intermediate obtained by means of a acid catalyst such as p-toluene sulfonic acid in an aromatic solvent at reflux, preferably xylene.
However, you can directly access compounds of formula (I) in which X represents a oxygen atom by reacting a compound of formula:
o / C ~
Ar OH

and an aromatic carboxylic acid of formula:
HN ~

O

the reaction being carried out in the presence of boric acid in an aromatic solvent at reflux, preferably the xylene.
In the latter case, the cyclization reaction is carried out "in situ" without isolating the condensate product intermediate tion.
The second embodiment of the process according to the invention can be represented by the diagram ~ 2S ~

following reaction:
Diagram II

Ar Q + ~ CH3 ~ ~ R ~

R2 (4) BrCH ~

Ar X ~ 4 (6) R2 AlCH2 ~ D` ~
(6) ~ oll Ar X ~ ~ OR4 (7) R2 Ar ~
, ~ OR4 (8) Q = OH or Cl X ~ NH, -O-or-S-Al = -P (V) 3 Br, V being an alkyl or an aryl oU -P- (W), W being aryl, alkoxy or aryloxy.
o - 12b -This method which is particularly pre-when when in the compounds of formula (I) Y represents the radical C} l, consists in reacting the acid derivative aromatic carboxylic of formula (1) on an acid ester aromatic carboxylic of formula (4) bearing in position 4 a methyl radical and an amino, hydroxy or thio group in position 3. The intermediate compound obtained (5) is then subjected to bromination leading to the bromo derivative methylated in position 4 (6). After reaction of a triaryl or trialkylphosphine, a triaryl or trialkylphosphite, or well of an aryl phosphine oxide one obtains the compound (7) which is then cyclized to the compound of formula (8) in the Wittig reaction conditions.
According to this method the cyclization reaction i.e. the transition from compound (7) to compound ~ 8) is carried out in the presence of a base which may be a hydroxide or an alkali metal carbonate for example lithine or potassium carbonate, an alkali metal hydride by example sodium hydride, an alkali metal alcoholate for example sodium methylate or tert-butoxide of potassium, a tertiary amine, for example triethylamine, di-isopropylethylamine or diazabicycloundecene (DBU) or an alkaline amide, for example sodium amide or lithium di-isopropylamide. The temperature of the reaction is between -10C and + 150C and we can use, as solvent, a dipolar aprotic solvent (dimethyl sulfoxide or dimethyl formamide), an alcohol, a ether (dioxane or tetrahydrofuran). The reaction is advantageously carried out in tetrahydrofuran (THF) between 0 C and 80 C using triethylamine or DBU
as a basis.
The bromination reaction, that is, obtaining tion of the compounds of formula (6) is carried out in the presence N-bromosuccinimide in an aromatic or chlorinated solvent - 12c -for example in benzene or car tetrachloride bone previously dried, the temperature being preferably rence comp.rise between 70C and 90C, the radical initiator being preferably benzoyl peroxide The acylation reaction, that is to say ~ the prep.ra-tion of the compound of formula (5), is carried out in the same conditions than those described above for diagram I.
The esters or acids obtained by the methods described above can be converted so classic in various analogues subject to signfica-li) to (i.ii), of the radical Rl.
So the saponification of esters gives the corresponding acids. These can be transformed to acid chlorides which are then easily converted in amides. These amides can also be obtained by direct action of amines on the esters obtained previously is lying. The reduction of esters, aldehydes or amides by a suitable reducing agent (e.g. aluminum hydride lithium) allows access to the corresponding alcohols and amines dants.
The compounds of formula (I) obtained by the process according to the invention can be transformed into salts. he can be either alkali or alkali metal salts earthy or organic amines when the compounds of formula (I) are in free acid form, se.
mineral or organic acid salts when compounds of formula (I) are in amine form free.
~, The invention relates in particular to the methods described in the experimental part which follows, for obtaining preferred compounds of the invention.
The present invention also relates to compounds cosmetic container, in a cosmetically support 8 ~; ~
- 12d -acceptable, at least one compound of formula (I), this composition in particular in the form of a lotion, gel, soap, shampoo or cream.
These compositions according to the invention are in particularly useful in body and hair hygiene and in particular to combat the oily appearance of the skin or hair ~
The concentration of compound (s) of formula (I), in the cosmetic compositions is between 0, ~ 005 and 2% by weight and preferably between 0.01 and 1% by weight.
The cosmetic compositions according to the invention may contain inert additives.
The compositions according to the invention can also contain preservatives, agents stabilizers, moisture regulating agents, agents pH regulators! pressure modifiers osmotic, emulsifying agents, UV-A filters and UV-B, antioxidants such as 1- ~ tocopherol, butyl-hydroxyanisole or butylhydroxy toluene.
We give below, by way of illustration and without any limiting nature, several examples of preparation of the compounds of formula (I) according to the invention as well as examples of compositions containing them.

2- (p-tert-Butylphenyl) -6- benzo ~ b) thiophene-methyl carboxylate.
a) 3- (p-tert-Butylbenzoylthio) -4-methyl benzoate methyl.
In 20 ml of dry THF is added successively 1.80 g ~ 10 mmol) of 3-mercapto-4-methyl benzoate methyl, l, llg (1.5 ml, 11 mmol) of triethylamine and 2.20 g (11 mmol) of p-tert-butylbenzoyl chloride. We shake 68 ~ i ~
- 12th -2 hours at 20C, remove this water (100 ml), and extract with dichlorome-thane (3xlOOml). The organic phase is dried and evaporates. It is then purified by passing over a short silica column t5Xlo cm) eluting with a mixture of dichloromethane (50 ~) and hexane (50 ~). C) n received on product with an Rf = 0.35 (eluent: dichloromethane).
The solvents are evaporated and thus 3- (p-tert-Butylbenzoylthio) -4-methyl methyl benzoate (3.08 g, 90 ~).
b) 4- ~ romomethyl-3- (p-tert-butylbenzoylthio) methyl benzoate. 2.80 g of the ester obtained in the example l (a) are dissolved in 20 ml of carbon tetrachloride dry, at reflux. 20 mg of benzoyl peroxide are added and, in portions, 1.45 g (8.15 mmol) of N-bromosuccinimide.
Heat at reflux for 10 hours, add 0.145 g (0.8 mmol) of N-bromosuccinimide, and still heats 4 hours at reflux. The solvents are evaporated and purified roughly the residue by passing through a short silica column (5x10 cm), eluting with dichloro-methane. We thus obtain a mixture of 3 pre-feeling Rf = 0.35; 0.40; 0.45. (eluent: dichloro-methane). These products are, for - 13 ~

decreasing polarity order: the starting product, the monobromo product and the dibromo product. The latter is removed by chromatography ("Waters ~" Prep 500, silica column, eluent: mixture of dichloromethane (50%) and hexane (50% ~.
This gives an oil (3.20 ~) containing approximately 80% of ester.
desired and about 2n% starting material.
c) methyl 2- (p-tert-Butylphenyl) -6-benzo (b) thiophenecarboxylate.
3.10 g of the mixture obtained in Example is dissolved in 20 ml of THF ~
l (b) and 1.85 g ~ 7mmol) of triphenylphosphine. It is heated to reflux under nitrogen for 4 hours, then re ~ roidit and a ~ drop 1.06 g (7mmol) diazabicycloundecene (DBU). When adding each drop we observe the transient appearance of a dark yellow color. At the end of the addition, we observe a slight precipitate. Heat at 50C for 15 minutes, pour into water (100 ml), extracted with dichloromethane (3X100 ml), dried and evaporated solvents. The desired product is obtained by chromatography (color.ne of silica, eluent: mixture of di ~ chloromethane (20%) and hexane (80%). The solid obtained is recrystallized from hexane. This gives 2- (p-tert-butyl phenyl) -6-benzo ~ b) methyl thiophenecarboxylate (1.60 g, 62% from the ester obtained in l (a)).
F: 155C; Rf = 0.70 (eluent: mixture of dichloromethane (20%) and hexane (80%)).

2- (p-tert-Butyl-phenyl) -6-ben ~ o (b) thiophenecarboxylic acid 1.2 g ~ 3.7 mmol) of the ester obtained in Example l (c) are suspended in 100 ml of a 2N sodium hydroxide solution in methanol. We heat 4 hours at reflux, pour into water (100 ml), acidify to pH 0 with chlorhy-concentrated dric, extracted with ethyl ether (3x100 ml), dry and evaporates. The solid obtained is recrystallized from acetonitrile. We obtain thus 2- (p-tert-Butylphenyl) -6-benzo (b) thiophenecarboxylic acid.
(1.05 g; 91%).
F: 318C. Rf = 0.7 (eluent: mixture of dichloromethane (80%) and methanol (20%)).

2- (5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl ~ -6-benzo (b) methyl thiophenecarboxylate.
a) 4-Methyl-3- (5,6,7,8-tetrahydro-5,5,8,8, -tétraméthy ~ -2-naphtoyl-thio) ~ ethyl benzoate.

* (trademark) BSB / JD / EL / ML BR.13347 Analogously to example l (a), starting from 1.83 g (lOmmol) of methyl 3-mercapto-4- ~ ethyl benzoate, l, Sml of triethylamine and 2 ~ 76 g ~ 11 mmol) of 5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- chlortlre naphthoyl, we get 4 ~ methyl-3- (5,6,7,8-tet ~ hydro-5,5,8,8-tetramethyl--2-naphthoylthio) methyl benæoflte. (3p50g; 88%) F: 120DC. R ~ = 0.7 (using dichloromethane as eluent).
b) 4-Bromomethyl-3- (5,6,7,8-tetrahydro- (5,5,8,8-tetramethyl-2-naphthoyl-thio) methyl benzoate.
Analogously to example l (b), starting from 3.30 g (8.3 mmol) ~ E the ester obtained in Example 3 ~ a), 1.48 g ~ E ~, 3 mmol) of N-bromosucci-nimide, and 20 mg of benzGyle peroxide, obtained after chromatography ("Waters" prep 500, silica column, eluent: dichloromethane mixture ~ 60%) and hexane (40%)), a mixture containing about 10% of starting and 90% of 4-bromomethyl -3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthoylthio) methyl benzoate. (2.50g).
c) In a manner analogous to example l (c), starting from 2.40 g of the mixture obtained in 3 (b) and 1.6 g of triphenylphosphine, in 15 ml of THF, obtains, after 6 hours reflux, a phosphonium salt which is immediately treated with 0.9ml of DBU. After treatment in a manner analogous to example l (c) and after chromatography (silica column, eluent: mixture of dichlorome-30% thane and 70% heptane) we obtain 2- (5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzo (b) methyl thiophenecarboxylate. (l, SOg 50%
from the ester obtained in 3a)).
F: 170C, Rf = 0.8 (eluent: dichloromethane) E ~ EMPLE 4 Acid 2- (5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzo-(b) carboxylic thiophene.
Analogously to Example 2, from 1.10 g (2.9 mmol) ester obtained in Example 3 (c), 2- (5,6,7,8-Tetrahydro-) acid is obtained

5,5,8,8-tetramethyl-2-naphthyl) -6-benzo (b) thiophene carboxylic. (0.99g, 93, F: 297QC, Rf = 0.7 (eluent: mixture of dichloromethane (80%) and methanol (20%)) -2- (p-tert-Butylphenyl) -6-benzo (b) methyl furannecarhoxylate.
a) methyl 3- (p-tert-Butylbenzoyloxy) -4-methyl benzoate.
Analogously to example l (a), from 3.30 g (20 mmol) of Methyl 3-hydroxy-4-methyl benzoate, triethylamine (2.20g, 22mmol) and BSB / JD / EL / Ml BR.13347 p-tert-butylbenzoyl chloride (3.90g, 20mmol) in 40ml of THF, we obtain methyl 2- (p-tert-butylbenzoyloxy) -4-methyl benzoate. (5.30g, 81%) Rf = 0.45 (eluent: mixture of ethyl ether (30%) and llexane (70%)).
b) methyl 4-Bromomethyl-3- (p tert-butylbenzoyloxy) benzoate.
Analogously ~ Example 1 (b), from 1.60 g (Smmol) of e ~ ter obtained in 5 (a), 1.30 g of N-bromosuccinlmide and peroxide of benzoyl (10 mg), dissolved in 5 ml of carbon tetrachloride and brought to reflux under a7.0te for 20 mnp, after chromatography (~ IPLC, "ZORB ~ X SIL *" column, eluent: dichloromethane (80%) hexane (20% ~) mixture, methyl 4-bromomethyl-3- (p-tert-butylbenzoyloxy) benzoate. (0.94g, 46%) F: 107C, Rf = 0.40 (eluent: mixture of ethyl ether (30%) and hexane (70%)) -c) Methyl 2- (p-tert-Butylphenyl) -6-benzo (b) furanecarboxylate.
Analogously to Example 1 (c ~, starting from OJ52g (1.30 mmol) ester obtained in Example 5 (b), and triphenylphosphine (0.40 g) in 2 ml of THF, is obtained, after heating at reflux for 4 hours under nitrogen, then DBU treatment (0.30 g) for 15 minutes ~ at 20C puls 15 minutes at reflux, the desired raw ester. ~ after purification (HPLC; "ZORBAX SIL" column, eluent:
mixture of diisopropyl ether (10%), heptane (gO%)), the 2- (p-tert-Butylphenyl) -6-benzo (b) methyl furannecarboxylate. (0.35g, 87%) F: 148C, Rf = 0.55 (eluent: ethyl ether mixture (30%) heptane (70%)).

2- (p-tert-Butylphenyl) -6-benzo (b) furanecarboxylic acid.
0.30 g (1 mmol) of ester obtained in Example 5 (c) are dissolved in 10 ml ethanol. 2ml of potassium hydroxide (5N) are added, and the mixture is heated for 2 hours at 50C. The precipitate obtained is dissolved by adding water (30ml), and 10 ml are added hydrochloric acid (N). Extracted with 150 ml of ethyl ether, washed with water until pH = 6 and evaporates. We obtain a residue ~ which is dried and dissolved in THF (20ml). By evaporation of THF, the acid 2- (p-tert-butylphenyl) -6-benzo (b) furannecarboxylic. (0.28g, 98%) -F: 294C, Rf = 0.60 (eluent: mixture of dichloromethane (80%) and methanol (20% 3).

2- (5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl 2-naphthyl) -6-benzo (b) -methyl furannecarboxylate.
a) ~ S 'methoxycarbonyl-2'-methylphén ~ 1-5,6,7,8-tetrahydro 5,5,8,8-te-tra-methyl-2-naphthoate.
* ~ trademark) BSB / JD / EL / ML BR. 13347 Analogously to Example 5 (a), apart from 3.32 g (20 mmol) of Methyl 3-hydroxy-4-methyl benzoate, and 5.51g (22mmol) of chloride 5 ~ 6 ~ 7 ~ 8 ~ -tetrahydro ~ 5 ~ 5 ~ 8 ~ 8-eetramethyl-2-naphthoyl ~ we obtain 5'-methoxy-carbOn ~ l-2 ~ methylphenyl-5,6,7,8-tétrahydro-5,5,8,8-tétram2thyl-2-naphtoate (7.1U ~, 93 ~ 1-F: 159C, Rf ~ 0.6 ~ eluent: mixture of ethyl Pther (50%), hexane (50 ~,)).
b) 2'-Bromomethyl-5'-me ~ loxycarbonyl-phenyl5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthoate ~
Analogously to example 5 (b), from 1.33 g (3.5 ml / l) d'es ~ er obtained in 7 ~ a), we obtain the 2'-bromométllyl-5 ~ -metho ~ ycarbon ~ l Fhenyl 5,6,7,3-tétrahydro-5,5,8,8-tétraméthyl-2-naphtoate 11,0 ~; ~, 6? ~).
F: 119C, Rf = 0.4 ~ eluent: ethyl ether mixture (30%), hexane (70%)).
c) Analogously to Example 5 (c), starting from OJ76g (1.66 mmol) ester obtained in 7 (b), 2- (5,6,7,8-tetrahydro-5,5,8,8-tetra-methyl-2-naphthyl-6-benzo (b) methyl furannecarboxylate. (0.5lg, 85%).
F: 112C, Rf = 0.55 (eluent: ethyl ether (30%), heptane (70%)).

EXE _ E 8 Acid 2- (5,6,7,8, -Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzo (b) furannecarboxylic.
Analogously to Example 6, 3.00 g (893 mmol) of the ester obtained in 7 (c), are treated with 200 ml of a sodium hydroxide solution in methanol (2N).
After 4 hours of heating at reflux, it is evaporated, poured into water (100 ml), acidifies pH 0 with concentrated hydrochloric acid, extralt with ether (3xlOOml), dries and evaporates. The residue is recrystallized from acetonitrile.
This gives 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzo (b) furannecarboxylic. (2.30g, 80 ~).
F: 280C, Rf = 0.75 (eluent: ethyl ether).

l-tert-Butoxycarbonyl-2- (p-tert-butylphenyl) -6-indolecarboxylate methyl.
a) methyl 3- (p-tert-Butylbenzamido) -4-methyl benzoate.
3.30g (20mmol) of methyl 3-amino-4-methyl benzoate dissolved in 40ml of THF, are treated at 0C with 3.9g (20mmol) of p-tert-butylbenzoyl chloride, in the presence of 2.2 g (20 mmol) of triethylamine. ~ almost 2 hours, we add 100ml of water, and the precipitate obtained is collected and washed with water (3xl00ml). We dries under vacuum and recrystallizes from carbon t ~ trachloride.
We obtain alnsi 3- (p-tert-butylbenzamldo) -4-methyl benzoate from BSB / JD / EL / ML BR.13347 , ~

methyl. (5.70g, 88%) F: 193 ~ C, Rf = 0.85 (eluent: ethyl ether).
b) 3 ~ -N (tert-Butoxycarbonyl) -p-tert-butylbenzamLdo ~ 4 methyl benzoate methyl.
0.97g (3mmol) of ester obtained in 9 (a) are dissolved in 5ml of THF and lml da DMF. We have ~ all 100 mg of sodlum hydride t80% in oil, 3.3 mmol) and stirred for 1 hour. We then have 0.72 g of ditertic dicarbonate butyl and stirred 2 hours at 20C. Then pour into water (100ml), extract with dichloromethane (3x50 ml), evaporate and dry. We recrystallize the residue obtained in cyclohexane. This gives the 3- ~ tert ~ butoxycar-bonyl-p-tert-butylbenzamido) -4-methyl methyl benzoate. (l, lUg, 86%).
F: 153C, Rf = 0.5 (eluent: ethyl ether mixture (5%), dichloromethane 95% ~) c) 4-Bromomethyl-3- (tert-butoxycarbonyl-p-tert-butylbenzamido) benzoate methyl.
4.30 g (10 mmol) of the ester obtained in 9 ~ b) are treated with 1.80 g (lOmmol) of N-bromo-succlnimide and 20mg of benzoyl peroxide, for 2 hours in refluxing carbon tetrachloride. 0.20 g of N-bromo- are added succinimide and heated to reflux for 1 hour. The solvent is evaporated off and filters the mixture on a short column of silica (5xlOcm), using as eluent a mixture of chloroform (90%) and hexane (10%).
After chromatography ~ "Waters" Prep 500, silica column, eluent: mixture ethyl ether (10%), dichloromethane (20%), hexane (70%)), we obtain ~
4-bromomethyl-3- (tert-butoxycarbonyl-p-tert-butylbenzamido) benzoate methyl. (3.60g, 71%).
F: 135C, Rf = 0.6 (eluent: dichloromethane).
d) l-tert-Butoxycarbonyl-2- (p-tert-butylphenyl) -6-indolecarboxylate methyl.
3.30 g (6.5 mmol) of the ester obtained in 9 (c) are dissolved in 20 ml of THF. 2.05 g (7.8 mmol) of triphenylphosphine are added and the mixture is heated to reflux 6 hours. Cool to 20C and a ~ jous 1.17ml (7.8mmol) of DBU. We heat 30 mir.utes at reflux, poured into water (100 ml), acidifies to pH 0 with a solution concentrated hydrochloric acid, extract ~ with dichloromethane ~ 3xlOOml).
After washing with water until neutral and drying, it is evaporated. The residue obtained is dissolved in dichloromethane and roughly purified by passage over a short column of silica (5xlGcm). We evaporate the solvarts and recrystallizes from cyclohexane. This gives the l ~ tert-butoxycarbonyl-Methyl 2- (p-tert-butylphenyl) -6-indolecarboxylate. (1.60g, 61%) F: 167C, R ~ = 0.7 (eluent: ethyl ether (50%), hexane (5U%)).

BSB / JD / EL / ML BR.13347 2- (p-tert-butylphenyl) -6-indolecarboxylic acid.
1.25 g (3.1 mmol) of the ester obtained in 9 (d) are agglued for 2 hours with 100 ml of sodium hydroxide in methanol (~), at reflux. We evaporate, taken up in water (100ml), extracted with ethyl ether (3xlQOml), acidifies the aqueous phase at pH 4 with a solu ~ ion of aclde ch] orhydrlque N. We extralt to ether (3xlOO ml), dry and é ~ apore the organic phase. The result obtained is recrystallized from acetonitrile. We get alnsi acid 2- (p-tert-butylphenyl) -6- indolecarboxylic. (0.75 g, 84%).
F: 297C, Rf = 0.5 (eluent: mixture of dichloromethane (80%) and methanol (20%)).

EXE ~ PLE 11 l-tert-Butoxycarbonyl-2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2--naphthyl) -6- methyl indole carboxylate.
a) 3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtamido) 4-methyl methyl benzoate.
Analogously to Example 9 (a), from 4.95 g, (30mmol) of methyl 3-amino-4-methyl benzoate and 2- (5,6,7,8-) chloride tetrahydro 5,5,8,8-tetramethyl) naphthoyl (7.50g, 30mmol), 3- (5,6,7,8-tec-trahydro-5,5,8,8-tetramethyl-2-naphtamido) methyl 4-methyl benzoate.
(~, 65g, 93%) -F: 159C9 Rf = 0.75 (eluent: mixture of dichloromethane (95%) and ethyl ether-(5%)).
b) 3-¦ N-tert-Butoxycarbonyl- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtamido) ¦ methyl 4-methyl benzoate.
Analogously to example 9 (b), one obtains, starting from 9.85 g (26mmol) of the ester obtained in ll (a), -3- ¦N tert-Butoxycarbonyl- (5,6,7,8-té
trahydro-5,5,3,8-tetra ~ ethyl-2-naphtamido) ~ 4-methyl methyl benzoate.
(8.50g, 67%) F: 132C, Rf = 0.8 (eluent: ethyl ether).
c) 4-Bromomethyl-3- [N-tert-butoxycarbonyl- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthamido)] methyl benzoate.
7.75 g (17.3 mmol) of ester obtained ~ in ll (b) are treated with 3.08 g of N-bromosuccinimide and 40 mg of benzoyde peroxide in 40ml of tetrachloride of carbon, at reflux, for 20 hours. It is evaporated to dryness, filtered on a short column of silica (5 × 10 cm), eluting with dichloromethane. We evaporates the solvents and purifies the re ~ idu by chromatography ("Waters"
Prep 500, silica column, eluent: ethyl ether mixture (5%) BSB / JD / EL / ML BR.13347 8 ~ i ~

dichloromethane (15%), and hexane (80%)). We thus obtain a mixture containing 20% starting material and 80% 4-bromomethyl-3-~ N (-tert-butoxycarbonyl- (5,6,7,8-tetrahydro-5,5,8, ~ -tetramethyl-2-naphtamido) ~
methyl benzoate. (7.2g).
d) 7.10 g of the mixture obtained in 11 (c) are dissolved in 40m1 of THF and trialted with 3 ~ 0g (12mmol) of triphenylphosphine. We heat 4 hours at reflux, cooling and aout 1.80g (12mmol) of DBU. Stir 2 hours at 20C.
After traling analogously to 9 (d) we obtain the 1-tert-butoxycarbonyl-2- (5,6,7,8ltetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -

Methyl 6-indole carboxylate. (3.80 g, 56% from the ester obtained in 11 (b)).
F: 162C, Rf = 0.6 ~ eluent: dichloromethane).

Acid 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) 6-indo-lecarboxyllque.
Analogously to Example 10, starting from 3.40 g (7.3 mmol) of the ester obtained in 11 (d), acid 2- (5,6,7,8-tetrahydro-5,5,8 ~ 8- is obtained) -tetramethyl-2-naphthyl) -6- indolecarboxylic. (2.30 g, 90%).
F: 215C, Rf = 0.6 (eluent: methanol mixture (20%), dichloromethane (80%)).

2- (5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-indolecarbo-methyl xylate.
1.60 g (4.6 mmol) of acid obtained in Example 12, are dissolved in 50m1 of methanol. 0.5 ml of concentrated sulfuric acid is added and the mixture is heated to reflux for 8 hours. The methanol is evaporated, taken up in dichlorome-thane (200ml) and wash with sodium bicarbonate solution. We collect the organic phase, dry and evaporate. The residue is purified by passing to through a short column of silica (5xlOcm), eluting with dichlorome-thane. This gives 2- (5,6,7 ~ 8-tétrahydro-5,5,8,8-tétramethyl-2-naph-tyl) -6-methyl indolecarboxylate. (1.60g, 96%).
F: 202C, Rf = 0.5 (eluent: mixture of ethyl ether (50%) and heptane (5 ~%)) -1-Methyl-2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-methyl indolecarboxylate.
1.40 g (3, Bmmol) of the ester obtained in Example 13, are dissolved in 20ml of dry T ~ IF, and treated with 0.14g (4.6mmol ~ sodium hydride (80% in BSB / J ~ fEL / ML BR.13347 oil). Qn stirred for 1 hour and added 0.65 g (4.4 mmol) of iodide methyl. Aglte for 2 hours, then pour into water (lO ~ II), extracted with dichloromethane (3xlOOml). The organic phase is dried and evaporated. The residue obtained is recrystallized from hexane. This gives l-methyl--2- (5,6,7, ~ -tétrahydro-5,5,8, ~ -tétraméthyl-2-naphty: L) -6- indolecarboxylate of ~ ethyle. (1.30 g, 91%).
F: 156C, ~ f = 0.65 (eluent: ethyl ether mixture (50%), hexane (50%).

L-methyl-2- acid (5,6,7 ~ 8-tetrahydro-5,5,8,8-tetramethyl-2-naph-tyl) -6-indolecarboxylic.
l, OOg ~ 2.65 mmol) of ester obtained in Example 14, are treated with analogous to example 12. This gives, after recrystallization in a mixture of ethyl acetate and isopropyl ether, 1-methyl-2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6- indolecarboxy-lique (0.9Og, 93%).
F: 256C, Rf = 0.8 (eluent: ethyl ether).

EXhMPLE 16 -Methyl 2- (p-tert-Butylphenyl) -5-benzimidazolecarboxylate.
a) methyl 4-Amino-3- (p-tert-butylbenzamido) benzoate.
1.65 g (lOmmol) of methyl 3,4-diaminobenzoate and l, lOg (llmmol) of triethylamine in 150 ml of ethyl ether are treated dropwise, to 0C per 2.00 g (10 mmol) of p-tert-butylbenzoyl chloride. We let come back at room temperature and stir for 1 hour. Pour into water (100ml), extract with dichloromethane (3xlOOml), dry and evaporate. We recrystallize in a mixture of isopropyl ether and cyclohexane. This gives 4-amino--3- (methyl p-tert-butyl-benzamido) benzoate. (2.40g, 73%) F: 175C, Rf = 0.6 (eluent: ethyl ether).
b) Methyl 2- (p-tert-butylphenyl) -5-benzimidazolecarboxylate.
2 g of the product obtained in 16 (a) are dissolved in lOGml of xylene, and 20 mg of p-toluenesulfonic acid (monohydrate) are added. We heat at reflux 16 hours ~ by removing water as it forms. We evaporate then the solvent, taken up in dichloromethane (100 ml), and washed with a saturated sodium bicarbonate solution. The organic phase is dried, the solvent evaporated and the residue purified by passage over a short column of silica (5xlOcm), eluting with a mixture of dichloromethane (95%) and ether ethyl (5%). The solvents are evaporated and the residue recrystallized from a mixture of cyclohexane and isopropyl ether. We thus obtain the ~ - (p-BSB / d ~ / EL / ML BR.13347 -tert-butylphenyl) -5-methyl benzimidazolecarboxylate. (1.40g, 74%).
F: 208C, Rf = 0.6 (eluent: ethyl ether).

EXE ~ LE 17 2- (p-tert-Butylphenyl) -5-benzimidazolecarboxylic acid.
1.20 g (3.9 mmol) of ester obtained in Example 16 (b) are stirred for 48 hours in 75ml of a sodium hydroxide solutlon in methanol (2N). The methanol is é ~ apore and 100ml of water is added. Extract with ether ethyl then acidifies to pH ~ with a hydrochloric acid solution (N). We extract with ethyl ether (3xl00ml), dry and evaporate. We recrystallize in a mixture of ethyl acetate and isopropyl ether. We thus obtain 2- (p-tert-butylphenyl) -5-benzimidazolecarboxylic acid. (0.70g, 61%). F:
212C, Rf = 0.6 (eluent: mixture of methanol (20%) and d ~ chloromethane (80%)).

2- (5,6,7,8-Tétrahydro-5,5,8, ~ -tétraméthyl-2-naphtyl) -5-benzimidaæo-methylcarboxylate.
a) 4-Amino-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtamido) methyl benoate.
Analogously to Example 16 (a), from 2.70 g (16.2 mmol) methyl 3,4-diaminobenzoate, and 4.05 g (16.2 mmol) chloride S16,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthoyl, after recrystallization, tallization in a mixture of ethyl acetate and isopropyl ether, the 4-amino-3- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphtamido) benzoate methyl. (5.20g, 84%).
F: 216C, Rf = 0.7 (eluent: ethyl ether).
b) In a similar manner to example 16 (b), starting from 5.00 g (13 mmol) of the ester obtained in Example 18 (a), 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -5-ber.zimidaæolecarboxylate. (3.70g, 78%).
F: 223C, Rf = 0.75 (eluent: ethyl ether) EXE ~ LE 19 Acid 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -5 ~ benzimidazolecarboxylic.
Analogously to Example 17, from 2.90 g (8 mmol) ester obtained in Example 18 (b), treated with 150 ml of a hydroxide solution sodium in methanol (2N) the acid 2- (5,6,7,8-tetrahydro-BSB / J ~ / EL / ML BR.13347 - 22 ~
\

~ 5,5,8,8-tetramethyl-2-naphthyl) -5-benzimld2zolecarboxylic. (2.40g, 86%).
F: 228C, R ~ = 0.6 (eluent: mixture of chloromethane (807O ~ methanol (20%)).

__ 2- (5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl 2naphthyl) -6-benzoxazole-carbo ~ ylate of me ~ hyle.
a) 3-Hydroxy-4-nitro benzoate of me ~ hyle.
36.6 g (0.2 ~ ole) of 3-hydroxy-4- acid are introduced into a flask nitro benzo ~ que, 40ml of methanol and 5.4ml of concentrated sulfuric acid. We heated at reflux for 8 hours, evaporated the millet: Leu reactlonnel, resumed residue by water, neutralizes and extracts with one liter of ethyl ether. We decant the organic phase, dry over magnesium sulphate, then evaporate. We recrystallizes the solid obtained from a hexane / cyclohexane mixture.
(38.5g, 97.7%) (F: 89C, RF = 0.55 (eluent: ethyl ether (50%) / hexane (50%)).
b) Methyl 4-amino-3-hydroxy benzoate.
5.9 g (0.03 mol) of 3-hydroxy-4-nitro are introduced into a flask methyl benzoate, 70 ml of ethyl alcohol and 10.1 g (0.18 mol) of iron powder. Cool to 10C and add dropwise 10ml of chlorhy-concentrated dric then stirred at room temperature for two hours. We filter the reaction medium, evaporate the filtrate. We take up the residue in water bicarbonate / ethyl ether, decant the organic phase9 dry over sulphate magnesium, then evaporates. The solid obtained is recrystallized from a mixture cyclohexane / isopropyl ether. (4.5g, 90%).
F: 121C, Rf = 0.55 (eluent: ethyl ether).
c) 3.34 g (0.02 mol) of 4-amino-3-hydroxy are introduced into a flask methyl benzoate, 4.6 g (0.02 mol) of the acid 5,6,7, ~ -tétrahydro-5,5,8,8-tétraméthyl-2-naphtolque, 1,23g (0,02mole) of acid boric and 200m1 of xylene. It is refluxed for 30 hours and separated the water formed with a Dean-Stark * We evaporate to dryness, take up Far de l'eau bicarbonate, and extracted with methylene chloride. We decent the phase organic, dried over magnesium sulfate and then evaporated. We purify the product by flash chromatography on a silica column, eluting with chloride methylene. It is crystallized from hexane (3.0 g, 41.3%).
F: 149C, Rf = 0.3 (eluent: hexane (70%) / ethyl ether (30%)) mixture.

EXE ~ LE 21 Acid 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl ~ -6-benzo-xazolecarboxylic.

* (trademark) BSB / ~ D / EL / ML BR.13347 ~ 6 ~

2.5 g (6.88 mmol) of the ester obtained in (C) in 200ml of methanolic sodium hydroxide (2M); It is heated at reflux for 4 hours, evaporates to dryness, takes up in water, acidifies to pH = 4 with chlorhy-concentrates, filters the solid which has precipitated and dries on anhydride phosphori ~ eu. Then recrystallized from a mixture of ethyl acetate / tetra-hydrofuran ~ (1.5g, 62.5% ~.
F: 310C, Rf-0.7 ~ eluent: ethyl ether) ~

Acid morpholide 2- (5,6,7,8, tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzoxazole carboxylic, a) Acid chloride 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzoxazole carboxylic.
6.98 g (20 mmol) of the acid obtained are introduced into a flask.
Example 21 in 100 ml of anhydrous dichloromethane. We have ~ 4 ml (20 mmol) of dicyclohexylamin & and stirred for 2 hours at 20C. We evaporate solvents and taken up in anhydrous ether. The salt thus obtained is filtered (10.5 g) which is used as is.
The salt is introduced into a flask and 100 ml of dichlo-dry romethane and 1.45 ml (20 mmol) of thionyl chloride. Shake for 4 hours at 20C, evaporate to dryness to obtain a white solid (7.25 g, 99%).
b) Morpholide of 2- (5,6,7,8-tetrahydro-5,5,8,8-téraméthyl-2- acid naphthyl) -6-benzoxazole carboxyllque.
1.05 ml (12 mmol) of morpholine is introduced into a flask and 50 ml of dichloromethane. 1.4 g (4 mmol) of the acid chloride obtained above dissolved in 50 ml of dichloromethane. We stir for 2 hours at 20C, throw into water, decant the organic phase, dries over magnesium sulfate, and evaporates the solvents.
Recrystallized from isopropyl ether to obtain 1.2 g of expected compound (72 ~ O). F: 149-150C.

Acid ethylamide 2- (5,6,7,8-tetrahydro-5 ~ 5,8,8-tetramethyl-2-naphthyl) -6-benzoxazole carboxylic.
Analogously to Example 22, starting from 12 mmoles of ethyla-mine, and 4 ~ moles of the acid chloride obtained in Example 22 (a), we obtain acid 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) ethylamide -6-benzoxazole carboxylic (1.1 g, 74 ~).
F: 164-165C (recrystallized from a mixture of ethyl acetate / isopro- ether pylic).
BSB / JD / EL / ML BR.13347 ~ 5 ~ 8 ~
EXE ~ LE 24 _. _ 2-hydroxyethyl ester of 2- ~ 5,6,7,8 tetrahydro-5,5,8,8 eetramethyl-2-naphthyl) -6- ben ~ oxazole carboxylic.
6.4 ml (114 mmol) of ethylene glycol are introduced into a flask, 1.9 ml (23 mmol) of pyridine and 50 ml of dlchlorométhane. We refrold at 0C
and add drop ~ drop 1.4 g (11 mmol) of the acid chloride obtained to Example 22 ~ a), dissolved in 50 ml of dichloromethane. Then shake 2 hours at 20C, throw in water, decant the organic plase, dry on magnesium sulfate, and evaporates the solvents. The product is quickly chromatographed on a silica column, using a mixture as eluent dichloromethane 90% / ether 10%. ~ 4.0 g; 91 ~).
: 126-127C

~ EXAMPLE 25 Alcohol 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6 ~
methyl benzoxazolyl.
50 ml of THF and 330 mg of nitrogen are introduced into a flask.
LiAlH4. 2.0 g (5 × 7 mmol) of the ester obtained are added in small amounts.
Example 20 (c) and refluxed for 1 hour.
It is treated with a solution of double sodium tartrate and potassium, filters, and collects the organic phase. It is dried over magnesium and evaporates the solvents. The residue obtained is purified by chromztography on a silica column in u ~ using a mixture of dichloromethane (95%) and ether (5%). The product is recrystallized from the cyclohexane. (1 g, 52%).
F: 125-126C.

2- L 3- (1-adamantyl) -4-methoxyphenyl acid methyl ester ~
-6-benzimicazole carboxylic a) 3- (1-adamantyl) -4-methoxybenzolque acid 5.4 ~ g (225 g g) of magnesium are introduced into a flask turnings, and 30 ml of THF. A solution of 48.3 g is added dropwise (150 mmol) of 2-adamantyl-4-bromo anisole, and 6 ml (70 mmol) of 1,2-dibromoethane in 300 ml of THF.
It is heated to reflux for 2 hours, cooled to -70C and a CC2 current for one hour. We let the temperature rise to 20C, throw into water, acidify to pH1 with concentrated hydrochloric acid, and extracted with ethyl ether. Decant the organic phase, dry on BSB / JD / EL / ML BR.13347 ~ 2S ~

magnesium sulfate and evaporates.
The solid obter-u is recrystallized from ethyl acetate (3.7 g, 86%) F: 238-239C
b) Chlorur ~ 3- (1-adamantyl) -4-methoxy-benzo acid ~ as.
200 ml of thionyl chloride are introduced into a flask, and a ~ o ~ lee in small quantities 35 g (122 mmol) of the acid obtained above. We reflux ~ until the gas evolution ceases. We evaporate to dryness, taken up in 100 ml of anhydrous benzene and evaporated to dryness. We get a $ n if the 3- (1-adamantyl) -4-methoxybenzo ~ acid chloride (37 g). F: 153-154C
that we use as is.
c) 4-amino-3- [3- ~ 1-adamantyl) -4-metho- ethyl ester ~ ethyl xybenzamido ~ -benzo ~ that.
3.32 g (20 mmol) of methyl ester are introduced into a flask 3,4-diaminobenzo ~ acid, 3.1 ml (22 ~ moles) of triethylamine and 100 ml anhydrous ether. A solution of chloride is added dropwise at 0 ~ C
of acid obtained above (6.1 g, 20 mmol), in 100 ml of ethyl ether. We let the temperature rise to 20C and stir for 2 hours. We throw in the water, decant the ethereal phase, dry over magnesium sulfate, and evaporate the solvents. The solid obtained is heated in 100 ml of isopropyl ether, at reflux for 15 min. It is left to return to 20 ° C. then filter. We thus obtain

7.4 g of a white solid which is used as it is for the rest of the synthesis.
d) Methyl ester of 2- ~ 3- (1-adamantyl) -4-methoxyphenyl acid ~ -5-benzimidazole carboxylic.
10.5 g (24 mmol) of the ester obtained are introduced into a flask above, 30 ml of xylene and 4.6 g (24 mmol) of p-toluenesulfonic acid.
The mixture is heated at reflux for 12 hours, separating the water formed. We evaporates to dryness, takes up the residue with a solution of sodium bicarbonate saturated.
The solid which is purified is filtered by column chromatography silica using as eluent a mixture of methylene chloride 95 ~ O
and 5% ether. The solvents are evaporated and a white solid is obtained which is briefly heated to reflux in 400 ml of ethyl acetate. We let cool and thus obtain the expected ester ~ 8.7 g: 87%).
F: 257-8 ~ C

EXE ~ LE 27 2- L 3- (1-adamantyl) -4-methoxyphenyl acid methyl ester ~
-6-benzoxazole carboxylic.
BSB / JD / EL / ML BR.13347 - 26 - ~ 2 ~~

a) 4-Amino-3- [3- (1-adamantyl) -4-methoxy- acid methyl ester benzoyloxy] -benzo ~ qUe-3.8 g ~ 30 mmol) of methyl ester of the 4-amino-3-hydroxybenzoq acid (3.5 ml t25 mmol) of trlethy are introduced into a flask: trlethy: Lamine and 100 ml of ether. We refro: ldit at 0C and ~ IJoute gout ~ e to drop 7 ~ (23 mmol) acidde chloride obtained in Example 26 (b) dissolved in 100 ml of ether ethyl. Then agitated at 20C for 4 hours, ~ ette in water, decanted the organic phase ~ dries on magnesium sulEate and evaporates. The residue obtained is recrystallized from cyclohexane. 8.5 g of product which is used as is for the following of: synthesis.
b) 2- L 3- (I-adamantyl) -4-methoxyphenyl acid methyl ester ~
-6-benæoxazole carboxylic.
8.5 g (20 mmol) of the eser obtained are introduced into a flask above, 400 ml of xylene and 3.7 g (20 mmol) of p-toluenesulfonic acid.
It is heated ~ e at reflux for 12 hours by separating the water formed. We evaporate at dry, take up the residue in a saturated sodium bicarbonate solution and filters the solid obtained which is purified by column chromatography silica using dichloromethane as eluent.
By recrystallization from a mixture of ethyl acetate and ether isopropyl, 7.7 g (95%) of the deslosed ester are obtained. F: 183-184C.

Aclde 2- [3- (1-adamantyl) -4-methoxyphenyl ~ -6-benzoxazole carboxy-lique.
6.4 g (15 mmol) of ester obtained are introduced into a flask Example 27 (b), and a solution of sodium hydroxide (16 g) in 300 ml of THF and 50 ml of water.
Agitation is carried out at ambient temperature for 72 hours, the solvents are evaporated, taken up in water, acidified to pH5 with hydrochloric acid N.
the solid obtained and washed with water. The solid is extracted with 7 liters of acetate ethyl, dried over magnesium sulphate and then evaporated. The solid is then treated with 500 ml of ethyl acetate, at reflux for 1 hour. We cool e ~ filters the solid (5.9 g, 95%), F: 312-314C

2- [3- (1-adamantyl) -4-decyloxyphenyl acid methyl ester ~
-6-benzoxazolecarboxylic.
a) 2- (1-adamantyl) -4-bromo-1-decyloxybenzen2.
3.2 g (104 mmol) of sodium hydride are introduced into a flask , BSB / JD / EL / ~ L BR.l3347 (80% in oil) and 100 ml of N, N-dimethylformamide. We add drop to drop a solution of 2-adamantyl-4-bromophenol (29 g, 95 mmol) in 100 ml of N, N-dimethylformamide, and agitates ~ until the gas evolution has ~
stopped. Then add 23 ml (104 mmol) of 1-iododecane and ag: Lte 8 ~ lures at 20C. We throw in water, dry over magnesium sulfate, and evaporate the brash. The product is purified by chromatography on a silica column, (eluent: heptane).
40.7 g (96%) of 2- (1-adamantyl) -4-bromo-l- are thus obtained.
decyloxybenzene. F: 69-70C.
b) 3- (1-adamantyl) -4-decyloxybenzo ~ acid.
Analogously to Example 26 (a), from 17.9 g (40 mmol) of the derivative obtained in Example 29 (a), after crystal-lization in a mixture of ethyl acetate and isopropyl ether, the acid 3- (1-adamantyl) -4-decyloxybenzo ~ that (13.5 g; 82%). F: 151-152C
c) 3- (1-adamantyl) -4-decyloxybenzolque acid chloride.
Analogously to example 26 (b), one obtains from 7.45 g (18 mmol) 3- (1-adamantyl) -4-decyloxybenzoic acid, 7.7 g of corresponding acid chloride (100 ~).
d) Methyl esters of 4-amino-3- L3- (1-adamantyl) -4-decy- acids loxybenzoyloxy ~ -benzo ~ que and 4 ~ C 3- (1-adamantyl) -4-decyloxybenzamid ~ -3-hydroxybenzo ~ that.
3.0 g (18 mmol) of methyl ester of 4-amino-3-hydroxybenzo ~ that acid, 2.8 ml (20 mmol) of triethylamine and 100 ml of ether. Cool to 0C and add dropwise a solution of acid chloride obtained above (7.7 gJ 1 ~ mmoles) in 50 ml of ether. We stirred at 20C for 2 hours, ~ was in water, decanted the organic phase, dries on magnesium sulphate and evaporates. Purified by chromatography on silica column, eluting with dichloromethane and thus obtains successively 2.2 g of the methyl ester of 4- C 3- (1-adamantyl) acid 4-decyloxybenzamido ~ -3-hydroxybenzoIque then 5 g of the methyl ester 4-amino-3-C 3- (1-adamantyl) -4-decyloxybenzoyloxy ~ benzoic acid.
e) 2- L3- (1-adamantyl) -4-decyloxyphenyl acid methyl ester ~
-6-benzoxazolecarboxylic.
6.8 g (12 mmol) of the mixture obtained are introduced into a flask above, 300 ml of xylene, and 2.3 g (12 mmol) of p-toluene acid sulfonic. The mixture is refluxed for 5 hours, separating the water which forms. We evaporated to dryness, taken up in a saturated solution of sodium bicarbonate, and extracted with dichloromethane. The organic phase is decanted, dried over magnesium sulfate and evaporates. The residue obtained is recrystallized from a BSB / JD / EL / ML BR.133 ~ 7 - 28 ~

mixture of ethyl acetate and isopropyl ether. 5.3 g are thus obtained.
(81%) 2- [3 ~ aclamantyl) -4-decyloxyphenyl ~ methyl ester -6-benzoxazole carboxylic. F: 127-128C.

EXE ~ LE 30 Acid 2- l 3- (1-adamantyl) -4-decyloxyphenyl ~ - 6-benzoxazolecarbo-xylic.
Analogously to Example 28, from 4.6 g (8.5 mmol) of the ester obtained in Example 29 (e), 3.9 g (88%) of acid are obtained 2-¦ 3- (1-adamantyl) -4-decyloxyp ~ enyl] -6-benzoxazolecarboxylic:
F: 200-201C (recrystallized from ethyl acetate).

2- ~ 3- (1-adamantyl) -4-methoxyphenyl acid ethyl ester ~
-6-benzo (b) furannecarboxylic.
a) 3- ~ 3- (1-adamantyl) -4-methoxybenzoyloxy acid methyl ester]
_6, _methylbenzolque.
Analogously to Example 5 (a), from 4.99 g (30 mmol) of 3-hydroxy-4-methylbenzGlque acid ester and of 9.14 g (30 mmol) of the acid chloride obtained in Example 26 (b), after chromatography on a silica column (eluent: dichloromethane mixture 50 7/50% hexam), 12 g of the desired ester (92%). F: 110C
b) 3- [3- (1-adamantyl) -4-methoxybenzoyloxy acid methyl ester ~
-4-bromomethylbenzolque.
Analogously to Example 5 (b), from 1.70 g (3.9 mmol) of ester obtained above, 0.70 g of ~ -bromosuccinimide and 20 mg of benzoyl peroxide in 15 ml of carbon tetrachloride brought to reflux 50us nitrogen for 3 hours, obtained after chromatography on silica column (eluent: mixture of 30% ethyl ether and 70% hexane) a mixture of the desired product and the starting product which is used as it is for the rest of the synthesis.
c) Methyl ester of 2- [3- (1-adamantyl) 4-methoxyphenyl3 -6- acid benzo (b) furannecarboxylic.
The mixture obtained above is dissolved in 100 ml of dry THF. Gold.
add 4.17 g (16 mmol) of triphenylphosp ~ ine and heat for 4 hours at reflux.
Cool to room temperature and add 2, ~ l ml (16 mmol) this diazabicycloundecene) (DB ~), drip. Shake 30 min at 35C after the end of addition, throw into water, acidify to pH 1 (with acid BSB / JD / EL / ML BR.13347 hydrochloric 6PI) and extracted with ether.
The organic phase is washed with water, dried over sulate of magnesium and evaporated ~
The residue is chromatographed on silica colum (eluent:
mixture of 20 Z ethyl ether and 80% hexane). I. Eluorescent fractions (under irradla ~ UV ion at 254 nm) are collected and the solvents evaporated. We thus obtains 1.82 g (27%, yield for steps 31 (b) and 31 ~ c) combined) of the desired ester. F: 180 ~ C

Acid 2- [3- (l-adamantyl) -4-methoxyphenyl ~ -6-ben ~ o (b) furannecarbo-xylic.
Analogously to Example 8, from 1.52 g (3.65 m ~ oles) of the ester obtained in Example 31 (c), 2- ~ 3 (1-adamantyl) acid is obtained -4-methoxyphenyl ~ -6-benzo (b) furannecarboxylic (1.32 g, 90%). F: 290C

2- ~ 3 (1-adamantyl) -4-methoxyphenylJ acid methyl ester -6-benzo (b) thiophenecarboxylic.
a) 4-¦ 3- (1-adamantyl) -4-methoxybenzoylthio acid methyl ester]
-4-methylbenzo; that.
Analogously to example l (a), starting from 5.47 g (30 mmol) of methyl 3-mercapto-4-methylbenzoate, 4.6 ml (33 mml) triethylamine, and 9.14 g (30 mmol) of the acid chloride obtained example 26 (b), we obtain the methyl ester of the acid 4- ~ 3- (1-adaman-tyl) -4-methoxybenzoylthio ~ -4-methylbenzolque (12.83 g, 95%). F: 140C
b) Methyl ester of 4- ~ 3- (l-adamantyl) -4-methoxybenzoylthio3 acid -4-bromomethylbenzolque.
Analogously to Example 1 (b), starting from 12.50 g (28 mmol) of the ester obtained above, 4.94 g (28 mmol) of N-bromosuccinimide and 100 mg of benzoyl peroxide, in 200 ml of carbon tetrachloride, after chromatography on a column of silica (eluent: 40% ethyl ether / hexane 60 7 mixture) ~ a mixture containing the starting material and the desired product which is used as is for the rest of the synthesis.
c) ~ methyl acid 2- 2- 3- (1-adamantyl) -4-methoxyphenyl) -6-ben ~ o (b) thiophenecarboxylic.
Analogously to example] (c), starting from the entire mixture obtained above, 4.55 g (17.5 mmol) of triphenylpllosphine, and BSB / JD / EL / PIL BR.13347 . - 30 -~. ~ 5g ~
2.60 ml (17.5 mmol) of DBU, one obtains, after chromatography on a column of SilicP ~ (eluent: dichloromethane 40% / hexane 60%) the desired ester (1.68 g; 14% - yield for steps 33 (b ~ and 33 ~ c) combined).
F: 172C

EXE ~ LE 34 Aclde 2- t 3- (1-adamantyl) -4 methoxyphenyl 1 -6-benzo (b ~ thiophene) carboxylic.
In a manner similar to Example 2, except for 1.32 g of ester obtained in Example 33 (c), 1.15 g (90%) of the corresponding acid are obtained.
F: 305C

_ 2- (3-tert-butyl-4-methoxyphenyl) -6-ben- methyl ester zo (b) furannecarboxylic.
a) 3-tert-butyl-4-methoxybenzolic acid.
Analogously to Example 26 (a), from 12.16 g (50 mmol) of 4-bromo-2-tert-butyl-methoxybenzene, 1.34 g (55 m ~ tome g) of magnesium, an excess of carbon dioxide, we obtain 8.31 g (80 ~) of acid 3-tert-butyl-4-methoxybenzolque with melting point 190C.
b ~ 3-tert-butyl-4-methoxybenzolque acid chloride.
Analogously to Example 22 (a), from 19, ~ g (92 mmol) of acid obtained above, of 18.3 ml (g2 ~ moles) of dicyclohexylamine, the salt obtained being treated with 6.7 ml (92 mmol) of thionyl chloride, 19.8 g (95%) of acid chloride (oil) are obtained.
~ pale alder), which is used as for the rest of the synthesis.
c) Methyl ester of 3- [3-tert-butyl-4-methoxybenzoyloxy acid ~
-4-methylbenæoIque.
Analogously to Example 5 (a), from 14.5 g (87 mmol ~ of methyl 3-hydroxy-4-methyl benæoate and 19.8 g (87 mmol) acid chloride obtained above, a ~ is obtained chromatography on silica column (eluent: 60% dichloromethane / 40% hexane mixture), the ester 3- ~ 3-tert-butyl-4-methoxybenzoyloxy ~ -4-methylbenzo ~
(27.7 g, 94 ~). F: 152C
d) 4-Bromomethyl-3- ~ 3-tert-butyl-4-metho- ethyl ester ~
xybenzoyloxy) -benzo ~ that.
Analogously to Example 31 (b), from 27.3 g (76.5 mmol) of ester above, and 13.6 g (76.5 mmol) of N-bromosuccinimide, using 100 mg of benzoyl peroxide as BSB / JD / EL / ~ L BR.13347 catalyst, after chromatography on a silica column (eluent:
mixture of dichloromethane 60% / hexane 40%), a mixture of the starting product and of monobrominated prGd-Iit, containing traces of dihromated product. This mixture is used as is for the rest of the synthesis.
e ~ Methyl ester of aclde 2- (3-tert-butyl-4-methoxyphenyl) -6-beIl-zo (b) furannecarboxylic.
The mixture obtained above (27.6 g) is dissolved in 100 ml of THF
dry. 16.6 g (63 mmol) of triphenylphosphine are added and the mixture is heated to reflux for 4 hours.
Cool to 20C, we have ~ 9.5 ml (63 m ~ oles) of DBU, drop to drop, under nitrogen. The addition finished ~ it is stirred for another 20 min at 80C. We ~ was in water, acidified to pH1 (with 6N hydrochloric acid) and extracted three times with 200 ml of dichloromethane.
The organic phase is washed with a saturated chloride solution of sodium, dried over magnesium sulfate, the solvents are evaporated and the residue ~ purified by silica column chromatography ~ eluent: mixture dichloromethane 40% / hexane 60%).
The fluorescent fractions are collected (under UV irradiation at 254 nm) and the solvents are evaporated to obtain the methyl ester of the acid 2- (3-tert-butyl-4-methoxyphenyl) -6-benzo (b) furancarboxylic (11.2 g, 43%). F: 179C

EXE ~ PLE 36 Acid 2- (3-te ~ t-butyl-4-methoxyphenyl) -6-benzo (b) furannecarboxy-lique.
Analogously to Example 8, from 7.64 g (22.5 mmol) of the ester obtained in Example 35 (e) treated with a mixture of methanol (500 ml) and aqueous sodium hydroxide (135 ml, 5N), the ac ~ of 2- (3-tert ~ butyl-4-methoxyphenyl) -6-benzo (b) furanecarboxylic (6.74 g, 92%). F: 235C.

2- ~ 3- (1,1-Dimethyldecyl) -4-methoxy- acid methyl ester phenyll -6-benzo (b) furannecarboxylic.
a) 4-bromo-2- (1,1-dimethyldecyl) -phenol.
A mixture of 2-methyl-1-undecene (35.6 g, 211 mmol), parabromophenol (36.6 g, 211 mmol) and Dowex * 50xl2 resin (100-200 mesh) previously washed with water, rinsed with acetone and dried in the oven for 3 hours G
80C, is heated to 100-110C for 48 hours. We re ~ cool z temperature * (trademark) BSB / JD / EL / ML BR.13347 - 32 ~

ambient and chromatography on a silica column (el ~ lant: dichloro- mixture methane 40% / hexane 60%), we thus obtain 4-bro ~ o-2- (1 ~ 1-dimethyldecyl) -phenol under the ~ elm of an oil ~ pale alder (30, ~ 5 g; 43%), The product is used as is for the rest of the synthesis.
b) 4-bromo-2- (l, l ~ dimethyldecyl) anisole The Obeenu compound above (30.85 g, 90 mmol) is dissolved in 100 ml of dry THF, then treated with 2.7 g (90 ~ moles) of sodium hydride (80%
in oil ~, which we have ~ out in small fractions. When the addition is complete, we stir 30 min at room temperature, then add 12.8 g (90 mmol) of iodide methyl. Stir 2 hours at 20C, evaporate the solvent, and purify the residue by chromatography on a silica column (eluent: dichloromethane mixture 40% / hexane 60%).
After evaporation of the solvents, the desired product is obtained under the form of an oil ~ alder (29.3 g, 91%).
c) 3- (1,1-Dimethyldecyl) -4-methoxybenzoic acid.
The brominated derivative obtained above (28.46 g, 80 mmol) dissolved in ~ 0 ml of dry THF, is added slowly to magnesium in turnings (2.34 g, 96 mAtg) and an iodine crystal. At the start of the addition, heat until that the reaction is initiated (establishment of a reflux). This ebb is then maintained by the rate of addition of the brominated derivative.
The addition finished, the stirring is continued for 30 min at 50C, cooled at 0C and passes a stream of carbon dioxide for 3 hours.
THF is then evaporated, 300 ml of water are added and acidified to p ~ l (using 6N hydrochloric acid). Extracted with 3 × 300 ml of ether ethyl. The organic phase is washed with a saturated NaCl solution, dried over magnesium sulfate, and the solvents evaporated.
The solid obtained is washed with 50 ml of cold hexane, and dried at the oven at 80C.
15.25 g of 3- (1,1-dimethyldecyl) -4- ~ ethoxybenzo acid are obtained;
(5g%). F: 112C
d) Acid chloride 3- ~ dimethyldecyl) -4-methoxybenzo; que.
Analogously to Example 22 (a), from 14.4 g (44.8 mmol) of acid obtained above, 9 ml (44.8 m ~ oles) of dicyclohexylamine, the salt obtained being treated with 3.26 ml ~ 44.8 moles) of thionyl chloride for 16 hours at 20 ~ C, the acid chloride is obtained raw used as is for the next step.
e) 3 ~ L 3- (1,1-Dimethyldecyl) -4-methoxy- acid methyl ester benzoyloxy ~ -4-methylbenzolque.
Analogously to Example 35 (c), from only 6.98 g (42 mmol) of methyl 3-hydroxy-4-methyl benzoate, all of the BSB / JD / EL / ~ L BR.13347 ~ 33 ~

crude acid chloride obtained in Example 27 (d), and 4.25 g (42 mmol) of triethylamine, the methyl ester of ~ 3 ~ L 3- (1,1-dimethyl-decyl) -4-methoxybenzoyloxy ~ -4-methylbenzo ~ that (17.84 g, 91% yield for steps 37 (d) and 37 (e) combined); in the form of a Yellow oil which crystallizes. F: 90C
f) Methyl ester of 4-bromomethyl- [3 - (1,1-climethyldecyl) -4- acid ~ ethoxybenzoyloxy ~ - benzoIque.
Analogously to Example 35 (d ~, from l7.4 g (37 mmol) of the ester obtained above, and 6.60 g (37 mmol) of N-bromosuccinimide, obtained after purification by chromatography on column (eluent: mixture of ethyl ether 40% / hexane 60 X), a mixture containing the desired monobromic product, the starting material, and traces of the dibromo derivative. C ~ mixture is used as is for the next step.
g ~ Methyl ester ~ 2- ~ 3- (1,1-dimethyldecyl) -4-methoxy- acid phenyl ~ -6-benzo (b) furannecarboxylic.
Analogously to Example 35 (e), starting from the entire mixture obtained above, 9.73 g (37 mmol) of triphenylphosphine and 5.5 ml (37 mmol) of DBUJ is obtained after three recrystallizations in hexane, 3.02 g of 2- L 3- (1,1-dimethyldecyl) -4- acid methyl ester methoxyphenyl ~ -6-benzo (b) furannecarboxylic 18% yield for all of steps 37 (f) and 37 (g) F: 95C

2- L 3- (1,1-Dimethyldecyl) -4-methoxyphenyl3 -6-benzo (b) furan- acid necarboxylic.
Analogously to Example 36, from 1.85 g (4 mmol) ester obtained in Example 37 (g), 2- ~ 3- (191-dimethyl-decyl) -4-methoxyphenyl ~ -6-benzo (b) furannecarboxylic (1.47 g, 82%).
F: 150C

EXE ~ IPLE 39 .
2- l 3- (1-adamantyl) -4-methoxyphenyl ~ -5-benzimidazole acid carboxylic.
7.8 g (19 mmol) of the ester obtained are introduced into a flask Example 26 (d ~ and 300 ml of 2N methanolic sodium hydroxide. Heating under reflux 24 hours, evaporates to dryness, takes up again with water, acidifies to pH5 with acid hydrochloric, filter the solid, and wash with water. The solid is then vacuum dried in the presence of P205. The solid is extracted with THF
(1 liter), then the THF is evaporated after filtration of the insoluble matter. The product BSB / J ~ / EL / ML BR.13347 ~ L r ~ I ~ 8 ~ i ~

is heated at reflux for 1 hour in a mixture of T ~ IF (300 ml) and ethyl acetate (300 ml). After cooling the solid is filtered and 7 g (93%) of 2- r3- (1-adamantyl) -4-methoxyphenyl ~ -5-benaei- acid are obtained midazolecarboxyliqIle. F: 358-359C.

EXE ~ IPLE 40 2- [3- (1-adamantyl-l ~ -hydroxyphenyl] acid methyl ester -5-benzimidazole carboxylic.
a) 2 ~ adamantyl) -4-bromo-tert-butyldlmét ~ yl ailoxybenzene.
30.7 g (100 mmol) of 2- (1-adamantyl) - are introduced into a flask 4-bromophenol, 15.4 ml (110 mmol) of triethylamine ~ 500 mg (4 ~ moles) 4- (N, N-dimethylamino) pyridine and 200 ml of T. ~ IF
Under nitrogen, a solution of 15.7 g is added dropwise (104 mmol) of tert-butyldimethylsilyl chloride in 100 ml of DMF on stir 4 hours, throw into water, extract with ether and decant the phase organic. After washing with water, drying over magnesium sulfate and evaporating ration of solvents, the residue obtained is purified by passage through a column of silica eluting with hexane.
3.62 g of the expected product are thus obtained. F: 111-112C.
b) 3- (1-adamantyl) -4-tert-butyldimethylsilyloxybenzo ~ acid.
1.18 g (48.8 mAtg) of magnesium are introduced into a flask and 50 ml of THF is added dropwise 13.7 g (32.5 mmol) of the product obtained above in 100 ml of THF, and heated at reflux for 2 hours.
Cooled to -78C and passed through the reaction medium carbon dioxide. Leave to return to room temperature, throw in water and acidifies to pH 1 with 5N hydrochloric acid.
ether and classl ~ eu treatment, the solid obtained is heated in 200 ml isopropyl ether at reflux.
After re ~ roidissement3 the solid is filtered and we thus obtain

8.2 8 (65%) 3- (1-adamantyl) -4-tert-butyldimethylsilyloxy benzolque acid ~
F: 245-246C.
c) 3- (1-adamantyl) -4-ter-butyldimethylsilyloxy acid chloride benzo ~ that.
6.45 g (16.7 mmol) of the acid obtained are introduced into a flask above, 3.3 ml (16.7 mmol) of dicyclohexylamine and 100 ml of chloride methylene. Stirred at room temperature for 2 hours, then add 1.35 ml (18.4 mmol) of thionyl chloride and stirred for 2 hours. We evaporate to dryness, taken up in 200 ml of ether, filters the dicyclohexylammonium chloride and evaporates the solvents. This gives 6.9 g of a sollde which is used as such "~
~ BSB / JD / EL / ~, BR.13347 what for the next step.
d ~ 4-Amino-3- L 3- (l-adamantyl) acid methyl ester - ~ -tert-butyl dimethylsilyloxy benzamido ~ -benzo ~ that.
2.77 g ~ 16.7 mmol are introduced into a flask) of 3,4-diamino-methyl benzoate, 2.6 ml (18.4 mmol) of triel: hylallline and 100 ml of ether. One solution is added dropwise: Lon 6.75 g (16.7 mmol) of chloride of acid obtained above in 100 ml of ether and stirred for 2 hours at 20C. Orl ~ was in water, extracted with methylene chloride, decanted the organ phase picnic, dry over magnesium sulfate and evaporate the solvents. The residue obtained is purified by passage over a silica column, eluting with a mixture 95% dichloromethane - 5% ether. 6.9 g are thus obtained (78% of the ester expected. F: 216-217C.
e) 2-L 3- (1-adamantyl) -4-tert-butyldime acid methyl ester thylsilyloxy phenyl ~ -5-benzimidaæole carboxylic.
6.3 g (11.6 mmol) of the product obtained are introduced into a flask above, 2.2 g (11.6 mmol) of p-toluene sulfonic acid and 100 ml of xylene. It is heated to reflux for 2 hours, evaporated to dryness, resumed with a saturated sodium bicarbonate solution, extract with methylene chloride, decant the organic phase, dry over magnesium sulfate and evaporate. We purifies the residue by passage over a silica column (eluent = mixture of dichloromethane 95% and ether 5 ~). 5.5 g (92%) of the ester are thus obtained.
expected. F: 277-278Co f) Methyl ester of 2- L 3- acid (1-adamantylt4-hydroxy pheny ~
-5-benzimidazole carboxylic.
5.2 g (10 mmol) of the ester obtained are introduced into UD flask above and 100 ml of THF We have ~ 11 ml dropwise (ll mmol) of a solution of tetrabutylammonium fluoride in THF (M) and stirred 2 hours. We throw into water, filter the solid, wash with water and extract with THF THF is evaporated and a white solid is collected which is heat in a mixture of 600 ml of ethyl acetate and 100 ml of THF On leaves to return to ambient temperature then filters the solid obtained (3.8 g;
95%). Y = 328-330C.

2- (5,6,7,8-tetrahydro-5,5,8,8, -tetra- methyl acid ester methyl-2-naphthyl) -6-benzothiazole carboxylic.
a) Methyl ester of 4-amino-3- (5,6,7J8-tetrahydro-5,5,8 ~ 8-té-acid traméhtyl-2-naphtoylthio benzo; que.
5.4 g (I4.8 mmol) of 4.4'-diami-BSB / JD / EL / ML BR.13347 no-3,3 'methyl dithiodibenzQate, 3.9 g (14.8 mmol) triphenyl phos-phine, 75 ml of dioxane and 5 ml of water. It is heated to reflux under nitrogen for 4 hours. Cooled to 20C and a ~ 6.2 ml drop by drop ~ 44.5 mmo ~ es) of triethylamine then 7J4 g (29.6 mmol) of 5,6,7,8-tet acid chloride trahydro-5,5,8,8-t ~ tramethyl-2-naphto ~ that dissolved in 50 ml of ether. We stick 1 hour at 20C, ~ ette the mixture in water, e ~ ether, decant &
organic phase, dried over magnesium sulfate and evaporated. We recrystallize in a mixture of isopropyl ether 66% - ethyl acetate 33% and obtains 8 g of the expected ester (68%). F: 15 ~ -155C.
b) Methic acid ester of 2- (5,6,7,8 - tetrahydro-5,5,8,8-tetramé -thyl-2-napthyl) -6-benzothiazole carboxylic.
9 g (22.6 ~ oles) of the ester obtained are introduced into a flask above, 4.3 g (22.6 mmol) of p-toluenesulfonic acid and 200 ml of xylene.
It is heated to reflux for 2 hours, evaporated to dryness, taken up in dichloromethane and wash with saturated sodium bicarbonate solution.
After usual treatment, a residue is obtained which is recrystallized from isopropyl ether. 8.2 g (95%) of the methyl ester are thus obtained.
2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzothiazole- acid carboxylic. F: 143-144C

Acid 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2 naphthyl) -6-benzo-thiazolecarboxylic.
5.6 g (14.7 mmol) of the ester obtained are introduced into a flask Example 41 (b), 200 ml of a 2N sodium hydroxide solution in methanol and 100 ml of THF Stir 4 hours at 20C, evaporate to dryness, take up in water and acidifies to pH5 with hydrochloric acid ~, filters the solid obtained wash with water until neutral. The solid is extracted with ether, dried over magnesium sulfate, evaporates and recrystallizes from ethyl acetate. We thus obtains 4 g (75%) of acid 2- (5,6,7,8-tetrahydro-5,5,8,8-eétraméthy -2-naphthyl) ~ 6-benzothiazolecarboxylic. F = 292-293C.

2- (4,4-Dimethyl-2,3-dihydro-1-benzo- acid methyl ester pyran-6-yl) -5-benzimidazolecarboxylic.
a) 4,4-Dimethyl-2,3-dihydro-1-benzopyran-6-carboxylic acid.
To a solution of sodium hydroxide (21 g) in 110 ml of water cooled to -5C, 9 ml of bromine are added dropwise. After 15 minutes, 6 g of BSB / JD / EL / ML BR.13347 6-acetyl-4,4-dimethyl-2,3-dihydro-1-ber.zopyranne in dioxane (50 ml).
Let rise ~ until 20C then heat up to 50C, we cools and has 70 ml of a solution of 9.2 g of sodlum metabisulfite then 42 m ~ of concentrated hydrochloric acid. We dilute ~ with water, fllter) wash the precipitate ~ until neutral. After crystallization from a mixture acetone-water, the expected acid is obtained with 90% yield.
b) Acid chloride 4,4-dimethyl-2,3-dihydro - l-benzopyran-6-carbo-xylic.
In a flask, 90 mg ~ 0.43 mmol ~ of the acid obtained at Example 42 (a) are suspended in 0.8 ml of dry dichloromethane.
87 ~ ll (0.43 mmol) of dicyclohexylamine are added dropwise and the reaction medium becomes clear. Stir 30 min at room temperature and a ~ 32 ~ 1 (0.43 mmol) of thionyl chloride.
After stirring overnight at room temperature, the dicyclohexylamine hydrochloride, evaporates dichloromethane and uses the product as is for the next step.
c) 4-amino-3- (4,4-dimethyl-2,3-dihydro-1-ben- methyl acid ester) zopyran-6-carboxamldo) -benzolque.
The crude product obtained above is dissolved in 2 ml of ether ethyl and a mixture of 72.5 mg (0.43 mmol ~ is added dropwise) 3,4-diamino benzoic acid methyl ester, 61 ~ 1 (0.43 mmol) triethylamine and 2 ml of ether.
Stir 2 hours at room temperature then throw in water (20 ml). Extracted by 3 ~ reactions of 10 ml of ethyl ether then the phase organic is washed with ~ ec a saturated solution of sodium hydride, dried on magnesium sulfate, filtered and then evaporated. The residue obtained is chromatographed phié on a silica column (eluent = 80% ether mixture - 20% hexane). We 82 mg (53%) of the expected product are thus obtained. F: 213C.
d) Fste ~ methyl acid 2- (4,4-dimethyl-2,3-dihydro-1-benzo-pyran-6-yl) -5-benzimidazole carboxylic.
The ester obtained above (82 mg;
0.23 mmol), 44 mg (0.23 mmol) p-toluenesulfonic acid monohydrate and 5 ml of xylene. The mixture is heated at reflux for 1 hour, re ~ roidi to 20C and chromatograph on a silica column (eluent = 80% ether - hexane 20%) -20 mg (26%) of the methyl ester of 2- (4,4 = -dimethyl-2,3-dihydro-1-benzopyran-6-yl) -5-benzimidazoleca ~ boxylic acid are thus obtained.
F: 110.115C

1 ~ BSB / JD / EL / ML BR.13347 :

. ~ ~ ~ 3 ~ 8 EXAMPLES OF COSMETIC COMPOSITIONS
Example 44 Cream Compound of example 4 ............. O, OOlg Stearyl alcohol ................. 3,000g Lanolin ........................... 5,000g Vaseline * .......................... I5,000g Distilled water qs .. ~ ............ lOO, OOOg Example 45: Oil cream in non-ionic water Compound of example 2 ............. O, OSOg Cietyl alcohol .................. 3,000g Steasyl alcohol ................. 3,400g Cetyl alcohol ~ xyethylenated (20 moles) .............. 0.630g Stearyl alcohol oxyethylenated (20 moles) ............. 1,470g Glycerol monostearate ........... 2,000g Vaseline oil. * ................ 15,000g Glycerin ......................... 10, OOOg Preserves & teas ........... ~ .............. qs Distilled water qs ................. lOO, OOOg In this example, the compound of example 2 can be replaced by the same amount of compound of Example 34.
Example 46: Cream Compound of Example 1 ............. 0.020g Isopropyl myristate ............ 81,700g Vaseline oil * fluid ........... 9, lCOg Ver. Silica produced by the company Degussa under the name of "Aerosil 200 *" .................... 9,180g In this example, the compound of Example l can be re ~ placed by the r ~ -re amount of compound of Example 35.

Example 47: Cream oil in anionic water Compound of Example 14 ........... O, OlOg Sodium dodecyl sulfate .......... 0.800g Glycerol ........................... 2,000g Stearyl alcohol ................ 20,000g Triglycerides of capric acids / caprylic sold by the company Dynamit ~ 'obel under the name of * (trade mark) BSB / JD / EL / ML BR.13347 - 39 ~ ~ 8 ~

"~ islyol 812 *." .................. 20,000g Preservatives ...................... ~ qs Demineralized water .............. lOO, OOOg Example 48: Gel Compound of example 19 ... .. 0, CC5g Hydroxypropyl cellulose sold by the company Hercules under the name of "Klucel HF * '' .............. 2,000g Water Jethanol (50:50) QSP ......... lOO ~ OOOg In this exe ~ ple, the compound of Example 19 can be replaced by the same amount of compound of Example 39.
~ xample 49: Skin lotion Comp ~ sé of example 19 ~ .... G, 005g Na2 HP04 0.1 ~ ................. 80,000ml NaH2 P4 0, lM .................. 20,000ml t 100 ~ of the particles of this compound must be of a diameter ~ less than Z5 microns.
This lotion is a suspension of pH = 7.4.
After packaging in an appropriate ampoule, the product is sterilized.
The product must be shaken vigorously before use.

* ~ brand of co ~ erce ~

BSB / JD / EL / ML BR.133 ~ 7 ''

Claims (27)

The embodiments of the invention, concerning the-which an exclusive property right or privilege is claimed, are defined as follows: 1. Characteristic heterocyclic aromatic compounds laughed at by the fact that they meet the general formula (I) (I) in which:
- R1 represents a radical -CH3 or -CH2OH
or a radical of formula in which R3 represents a hydrogen atom, a radical of formula -OR4, in which R4 represents a hydrogen atom, an alkyl radical having from 1 to 20 carbon atoms or a mono or polyhydroxy radical alkyl, or R3 represents the radical of formula - in which r 'and r "represent a hydrogen atom, a radi-cal lower alkyl or taken together form a heterocycle, - R2 represents a hydrogen atom or a radical -CH3, - Ar represents an aromatic radical chosen from the group consisting of radicals of formulas (A), (B), (C) or (D) defined below:

(AT) (B) in which Z represents an oxygen or sulfur atom, (VS) in which R5 represents a lower alkyl radical, and (D) in which R6 represents a hydrogen atom or a alkyl radical having from 1 to 10 carbon atoms and R7 represents has a branched alkyl radical having 4 to 12 atoms carbon or a cycloalkyl radical.
- Y represents a group = CH- or an atom nitrogen, and -X represents an oxygen atom, an atom of sulfur or a radical of formula? N-R8 in which R8 represents a hydrogen atom, a lower alkyl radical or a lower alkoxycarbonyl radical, provided on the one hand that when Y represents a group-ment = CH- and X represents an oxygen or sulfur atom, Ar is different from a radical of formula (C) in which R5 represents a radical -CH3 and on the other hand that when Y represents a nitrogen atom and X represents a atom of oxygen, Ar is different from a radical of formula (C) or of formula (D) in which R6 represents a radical alkyl having from 1 to 4 carbon atoms and R7 represents a branched alkyl radical having from 4 to 12 carbon atoms. 2. Compounds according to claim 1, characterized by the fact that the lower alkyl radical is a radical having 1 to 6 carbon atoms and is selected from the group consisting of methyl, ethyl, isopropyl, butyl and tert-butyl. 3. Compounds according to claim 1, characterized by the fact that the lower mono-hydroxyalkyl radical is a radical having 2 or 3 carbon atoms. 4. Compounds according to claim 1, characterized by the fact that the lower mono-hydroxyalkyl radical is chosen from the group consisting of radicals 2-hydroxyethyl and 2-hydroxypropyl. 5. Compounds according to claim 1, characterized by the fact that the polyhydroxyalkyl radical is chosen from the group consisting of radicals derived from glycerol, pentaerythritol and mannitol. 6. Compounds according to claim 1, characterized by the fact that the lower alkoxycarbonyl radical is chosen from the group consisting of methoxy carbonyl, ethoxy carbonyl, isopropoxy carbonyl and tert-butoxy carbonyl. 7. Compounds according to claim 1, characterized by the fact that the radicals r 'and r ", taken together, form-a heterocycle chosen from the group consisting of piperidino radical, piperazino radical, mor-pholino and the pyrrolidino radical. 8. Compounds according to claim 1, characterized by the fact that the cycloalkyl radical is chosen from the group consisting of the cyclohexyl radical, the radical 1-methylcyclohexyl and the adamantyl radical. 9. Compounds according to claim 1, characterized by the fact that they correspond to formula (II):

(II) in which:
-R1 represents the radical -CH2OH or a radical of formula in which R3 represents a radical of formula -O R4 in which R4 represents a hydro-gene, a radical -CH3 or -CH2CH2OH, or a radical of formula in which r 'and r ", identical or different, represent a hydrogen atom, a lower alkyl radical or taken together form a morpholino cycle, y represents a group = CH- or a nitrogen atom, and - X represents a sulfur atom, an atom of oxygen or a radical of formula> N-R8 in which R8 represents a hydrogen atom, the radical -CH3 or the radical -CO2 tert-butyl. 10. Compounds according to claim 1, character-laughed at by the fact that they correspond to formula (III) (III) in which:
- R4 represents a hydrogen atom or a radical -CH3, - Y represents a group = CH- or an atom nitrogen, and - X represents a sulfur atom, an atom of oxygen or a radical of formula? N-R8 in which R8 represents a hydrogen atom or a -CO2 tert-butyl radical. 11. Compounds according to claim 1, charac-terrified by the fact that they correspond to formula (IV):

(IV) in which:
- R4 represents a hydrogen atom or a radical CH3, - R6 represents a radical -CH3 or C10H21, - R7 represents a tert-butyl radical, 1,1 dimethyl decyle or adamantyle, - Y represents a group = CH- or an atom nitrogen, and - X represents a sulfur atom, an atom of oxygen or a radical of formula? N-R8 in which R8 represents a hydrogen atom. 12. Compounds according to claim 1, charac-cherished by the fact that they are chosen from the group consisting of:
- 2- (p-tert-butylphenyl) -6-benzo (b) thiophenecarboxylate methyl, - 2- (p-tert-butylphenyl) -6-benzo (b) thiophenecarboxylic acid, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzo (b) methyl thiophenecarboxylate, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- acid naphthyl) -6-benzo (b) -thiophenecarboxylic, - 2- (p-tert-butylphenyl) -benzo (b) furannecarboxylate methyl, - 2- (p-tert-butylphenyl) -benzo (b) furanecarboxylic acid, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -Methyl 6-benzo (b) -furanecarboxylate, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- acid naphthyl) -6-benzo (b) furannecarboxylic, - 1-tert-butoxycarbonyl-2 (p-tert-butylphenyl) -6-indole-methyl carboxylate, - 2- (p-tert-butylphenyl) -6-indolecarboxylic acid, - 1-tert-butoxycarbonyl-2- (5,6,7,8-tetrahydro-5,5,8,8-methyl tetramethyl-2-naphthyl) -6-indole carboxylate, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-indolecarboxylate methyl, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-indole acid carboxylic, - 1-methyl-2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-indole methyl carboxylate, - 1-methyl-2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6- acid indolecarboxylic, - methyl 2- (p-tert-butylphenyl) -5-benzimidazole carboxylate, - 2- (p-tert-butylphenyl) -5-benzimidazole carboxylic acid, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -benzimidazole-methyl carboxylate, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -benzimidazole- acid carboxylic, - 2- (5,6,7,8 tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzoxazole-methyl carboxylate, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzoxazole- acid carboxylic, - the acid morpholide 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naph-tyl) -6-benzoxazole carboxylic, - 2- acid ethylamide (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naph-tyl) -6-benzoxazole carboxylic, - 2-hydroxyethyl ester of 2- (5,6,7,8-tetrahydro-5,5,8,8-tetra- acid methyl-2-naphthyl) -6-benzoxazole carboxylic, - alcohol 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) -6-benzoxazolyl methyl, - the methyl ester of 2- [3- (1-adamantyl) -4-methoxyphenyl] -5-benzi- acid carboxylic midazol, - the methyl ester of 2- [3- (1-adamantyl) -4 methoxyphenyl] -6-benzo- acid carboxylic xazole, - 2- [3- (1-adamantyl) -4-methoxyphenyl] -6-benzoxazole carboxylic acid, - the methyl ester of 2- [3- (1-adamantyl) -4 decyloxyphenyl] -6-ben- acid carboxylic zoxazole, - 2 [3- (1-adamantyl) -4-decyloxyphenyl] -6-benzoxazole carboxylic acid, - the methyl ester of 2- [3- (1-adamantyl) -4-methoxyphenyl] -6-benzo- acid (b) carboxylic furan, - 2- [3- (1-adamantyl) -4-methoxyphenyl] -6-benzo (b) furan carboxy acid-- lique, - the methyl ester of 2- [3- (1-adamantyl) -4 methoxyphenl] -6-benzo- acid (b) carboxylic thiophene, - 2- / 3- (1-adamantyl) -4-methoxyphenyl / -6-benzo (b) acid -thiophene carboxylic, - the methyl ester of 2- (3-tert-butyl-4-methoxy- acid) phenyl) -6-benzo (b) carboxylic furan, - 2- (3-tert-butyl-4-methoxyphenyl) -6-benzo (b) furan acid carboxylic, - the methyl ester of 2- / 3- (1,1-dimethyldecyl) -4- acid methoxyphenyl / -6-benzo (b) carboxylic furan, - 2- / 3- (1,1-Dimethyldecyl) -4-methoxyphenyl / -6- acid benzo (b) carboxylic furan, - 2- / 3- (1-adamantyl) -4-methoxyphenyl / -5-benzimidazole acid carboxylic, - the methyl ester of 2- / 3- (1-adamantyl-4-hydroxy-) acid phenyl / -5-benzimidazole carboxylic acid, - the methyl ester of 2- (5,6,7,8-tetrahydro-) acid 5,5,8,8-tetramethyl-2-naphthyl) -6-benzothiazole carboxylic, - 2- (5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- acid naphthyl) -6-benzothiazolecarboxylic, and - the methyl ester of 2- (4,4-dimethyl-2,3-dihydro-) acid - 1-benzopyran-6-yl) -5 benzimidazole carboxylic. 13. Process for the preparation of compounds aromatic heterocyclics having the general formula (I):

(I) in which:

- R1 represents a radical -CH3 or -CH2OH
or a radical of formula in which R3 represents a hydrogen atom, a radical of formula -OR4, in which R4 represents a hydrogen atom, an alkyl radical having from 1 to 20 carbon atoms or a mono or polyhydroxy radical alkyl, or R3 represents the radical of formula - in which r 'and r "represent a hydrogen atom, a radi-cal lower alkyl or taken together form a heterocycle, - R2 represents a hydrogen atom or a radical -CH3, - Ar represents an aromatic radical chosen from the group consisting of radicals of formulas (A), (B), (C) or (D) defined below:

(AT) (B) in which Z represents an oxygen or sulfur atom, (VS) in which R5 represents a lower alkyl radical, and (D) in which R6 represents a hydrogen atom or a alkyl radical having from 1 to 10 carbon atoms and R7 represents has a branched alkyl radical having 4 to 12 atoms carbon or a cycloalkyl radical.
- Y represents a group = CH- or an atom nitrogen, and -X represents an oxygen atom, an atom of sulfur or a radical of formula? N-R8 in which R8 represents a hydrogen atom, a lower alkyl radical or a lower alkoxycarbonyl radical, provided on the one hand that when Y represents a group-ment = CH- and X represents an oxygen or sulfur atom, Ar is different from a radical of formula (C) in which R5 represents a radical -CH3 and on the other hand that when Y represents a nitrogen atom and X represents a atom of oxygen, Ar is different from a radical of formula (C) or of formula (D) in which R6 represents a radical alkyl having from 1 to 4 carbon atoms and R7 represents a branched alkyl radical having from 4 to 12 carbon atoms, characterized by the fact that it consists in reacting a aromatic carboxylic acid derivative of formula (1):
(1) in which Ar has the previous meaning and Q represents an OH radical or a chlorine atom, (a) either on a carboxylic acid derivative of formula (2):

(2) in which R2 and R4 have the meanings precedences and X
represents a group? NH, -O- or -S-, and to carry out a dehydrating cyclization reaction of the compound obtained in presence of an acid catalyst;
(b) either on a carboxylic acid derivative of formula (4):

(4) in which R2 and R4 have the previous meanings and X
represents a group? NH, -O- or -S-, and to carry out a bromination of the methyl substituent in position 4 of the compound obtained naked and then cyclized according to the conditions of the reaction Wittig the intermediate compound carrying a phospho- group nium or phosphinyl;
and, if desired, to transform, according to known methods, the-said compounds obtained with a view to obtaining any of the other meanings of the radical R1. 14. Method according to claim 13, characterized by the fact that it consists in carrying out an acyla-tion between a compound of formula:
in which Ar has the meaning given to the claim tion 13 and a carboxylic acid ester of formula:
in which R2 has the meaning given to the claim tion 13, R'4 represents an alkyl radical having from 1 to 20 carbon atoms and X 'represents a group? NH or -S-, then to a dehydrating cyclization of the intermediate using p-toluene sulfonic acid in an aro- solvent matic. 15. The method of claim 14, character-laughed at by the fact that dehydrating cyclization is carried out in xylene at reflux. 16. The method of claim 13, character-laughed at by the fact that it consists in reacting a compound of formula:
in which Ar has the meaning given to the res-dication 13, and an aromatic carboxylic acid of formula:
in which R2 has the meaning given to the claim tion 13, in the presence of boric acid in an aromatic solvent. 17. The method of claim 16, character-laughed at by the fact that the reaction is carried out in xylene at reflux. 18. Method according to claim 13, charac-terrified by the fact that the bromination of the intermediate compound is performed in the presence of N-bromosuccinimide in a aromatic or chlorinated solvent. 19. The method of claim 18, charac-terrified by the fact that the bromination is carried out in benzene or carbon tetrachloride at a temperature between 70 and 90 ° C. 20. The method of claim 13, character-laughed at by the fact that the intermediate derivative carrying a phosphonium or phosphinyl group corresponds to the formula following (7):

(7) in which Ar, X, R2 and R4 have the given meanings in claim 13 and A1 represents a radical of formula -? (V) 3 Br- in which V represents an alkyl radical or aryl, or a radical of formula -? - (W) 2 in which W represents an aryl, alkoxy or aryloxy radical. 21. The method of claim 20, character-laughed at by the fact that the cyclization of the intermediate derivative carrying a phosphonium or phosphinyl group of formula (7) according to claim 20 is carried out in presence of a base in a dipolar aprotic solvent, an alcohol or an ether, at a temperature between -10 ° C and + 150 ° C. 22. The method of claim 21, charac-terrified by the fact that the dipolar aprotic solvent is is dimethyl sulfoxide or dimethyl formamide. 23. The method of claim 21, charac-terrified by the fact that the ether is dioxane or tetrahydrofuran. 24. The method of claim 21, 22 or 23, characterized in that the cyclization is carried out in tetrahydrofuran between 0 ° C and 80 ° C using the triethylamine or diazobicycloundecene as the base. 25. The method of claim 13, for the preparation of the compounds corresponding to the general formula (II):
(II) in which R1 represents a radical -CH2OH or a radical of formula in which R3 represents a radical of formula -O R4 in which R4 represents a hydrogen atom, a radical -CH3 or a radical -CH2 CH2OH, or a radical of formula in which r 'and r ", identical or different rents, represent a hydrogen atom, an alkyl radical lower or taken together form a morpholino cycle, Y represents a group = CH- or a nitrogen atom and X
represents a sulfur atom, an oxygen atom or a radical of formula? N-R8 in which R8 represents a hydrogen atom, -CH3 radical or -CO2 tert- radical butyl; characterized in that in the derivative of formula (1) Ar represents a radical and Q represents an -OH radical or a chlorine atom, and in the derivative of formula (2) or (4), R2 represents an atom of hydrogen, R4 represents a hydrogen atom, a radical -CH3 or a radical -CH2CH2OH and X represents an atom of sulfur, an oxygen atom or a radical of formula? N-R8 in which R8 represents a hydrogen atom, a radical methyl or a tert-butyl CO2 radical. 26. The method of claim 13, for the preparation of the compounds of general formula (III):
(III) in which R4 represents a hydrogen atom or a radical -CH3, Y represents a group = CH- or a nitrogen atom and X represents a sulfur atom, an oxygen atom or a radical of formula? N-R8 in which R8 represents an atom of hydrogen or a -CO2 tert-butyl radical, characterized by the fact that in the derivative of formula (1), Ar represents the radical and Q represents an -OH radical or a chlorine atom, and in the derivative of formula (2) or (4), R2 represents an atom of hydrogen, R4 represents a hydrogen atom or a radical -CH3 and X represents a sulfur atom, an oxygen atom or a radical of formula? N-R8 in which R8 represents a hydrogen atom or a -CO2-tert-butyl radical. 27. The method of claim 13, for the preparation of the compounds corresponding to formula (IV):
(IV) in which R4 represents a hydrogen atom or a radical -CH3, R6 represents a radical -CH3 or -C10H21, R7 represents a tert-butyl, 1,1-dimethyl decyl or adamantyl radical, Y represents a group = CH- or a nitrogen atom and X
represents a sulfur atom, an oxygen atom or a radical of formula? N-R8 in which R8 represents an atom of hydrogen, characterized in that in the derivative of formula [1) Ar represents a radical of formula in which R6 represents a radical -CH3 or -C10H21 and R7 represents a tert-butyl radical, 1,1-dimethyl decyl or adamantyl, and Q represents an -OH radical or an atom of chlorine, and in formula (2) or (4), R2 represents a hydrogen atom, R4 represents a hydrogen atom or a radical -CH3 and X represents a sulfur atom, a oxygen atom or a radical of formula? NH.